Update 12-22-11 – If you use a Pitch block in one of the rows, be sure to set the Pitch Source to Local Mono. If you don’t, signal from the other input will feed into the wrong row and sound funky! Thanks to Bakerman on the forum for this tip.
UPDATE 12-19-11 – You can use Volume blocks instead of Mixer blocks (thanks to Stringer76 on the forum). I’ll show this at the bottom of the article. I’ll also show using 2 Amp blocks.
For years I’ve been playing Ernie Ball John Petrucci guitars both because I’m a huge Dream Theater fan and because it’s such a great guitar! Playing music on Oahu, there is always a demand for an Acoustic Guitar sound. I knew I wanted to play an Electric Guitar and have certain chorus cleans and distortion tones, but I didn’t want to switch back and forth between an electric and acoustic. Ernie Ball guitars have a Piezo option which includes a 2nd pickup system that has a separate output and creates an acoustic guitar sound.
You can either blend the 2 sounds from the guitar into the same cable/signal, but acoustic guitar usually doesn’t sound good through an electric guitar setup. So you have the option of running 2 cables (or a specialized Y cable) to separate the electric and acoustic sounds to different amps. This is where it gets really cool as you can blend the two distinct sounds together, similar to how a keyboardist might blend piano and strings, for example.
Usually people send the electric signal to their electric rig (effects, amp, cab) and the acoustic signal to an acoustic amp or to the PA system. You have separate volumes for each sound and can blend the 2 sounds to your liking. I usually use a dry acoustic tone and a chorus clean electric blended for a very full-sounding clean tone.
My rig used to be a Mesa Boogie Roadster with 2×12 Lonestar cab and the TC Electronic G-system for the electric sound, and a Presonus Eureka preamp into a JBL EON 15 powered speaker. I definitely carried the most gear compared to other guitarists here! It sounded great and I’d probably still be using that rig today, until the Axe-FX came along. The Axe-FX quickly replaced my electric rig, but I still used the Eureka preamp for my acoustic sound. I knew there was a way and finally figured out how to run both signals into my Axe-FX Ultra, since there are multiple inputs and outputs. Suddenly the gear I needed was cut down and I only needed the Axe-FX and a powered speaker! I posted a video of my previous patch setup using the Axe-FX Ultra.
I have since refined the setup since getting an Axe-FX II, and I believe you can still do everything I do here on the Axe-FX and Axe-FX Ultra. My setup talks about using a single guitar with 2 outputs, but this method can be applied to 2 separate guitars as well with a few additions. Anything below that talks about my acoustic or piezo signal can be your 2nd guitar.
First let’s talk about I/O settings. I prefer to use Input 1 only instead of using Input 1 for electric and Input 2 for acoustic. One of my favorite features of the Axe-FX is Copy Out1 to Out2, found on the Audio tab of the I/O menu.  This gives me a volume knob for the signal sent to the PA system using Output 1 and a volume knob for the identical signal sent to my powered speaker using Output 2.  Using Input 2, you lose this functionality and you have to put an FX Loop block in each patch.  I can set Output 1 for the PA and still adjust my own stage volume without changing the gain staging for FOH.

I also use the Instrument Input on the Front Panel for the electric and Input 1 Right on the Rear Panel for the acoustic.  The main reason for this isn’t the “special sauce” on the front input, but so I can have 2 separate input volumes that the Axe-FX II offers.  (Sorry Ultra and Standard owners; the front and rear inputs share the same physical volume knob.) My Piezo signal is usually hotter than the electric singal, so I like that I can tailor each input as needed.  Depending on your setup, you might be able to just use the rear inputs and the Input 1 volume and not worry about getting a cable to the front of the Axe-FX.

Then you just set Input 1 Mode to Stereo on the Audio page of the I/O menu.  It’s very important that you know that now your Electric signal is Input 1 Left and your Piezo signal is Input 1 Right.  You can have your output mode as Mono or Stereo and you’ll still get both signals after we finish our patch setup.  I ran a mono output for years, and just recently started running stereo.
Now on to the patch. Start with a blank patch and add shunts all the way across Row 1 and Row 2.  We are going to have separate signal paths so each guitar has its own effects and tone shaping.  Since most of the presets on the Axe-FX start with Row 2, I have chosen to leave Row 2, 3 and 4 for my electric guitar sound.  Row 1 will be for my acoustic sound. This might get confusing later, so heads up.

Next, go to the Input/Gate tab in Layout and turn this gate off by turning the Threshold to Off.  This is due to something I didn’t realize in my previous video and setup. Since I am using Input 1 for both guitars, the Input Gate is shared for both signals.  On a clean patch this may not be a problem.  But on a high gain patch, I would play my acoustic signal only, and I would hear noise from the electric row. I adjusted the Input Gate to get rid of that noise, but then it was clamping down too hard on the acoustic sound.
I realized each source needs its own Noise Gate, therefore allowing me to turn off the Input Gate. More on this later.

NOTE – This next section talks about using 2 Mixer blocks.  Since this posting, I actually now recommend using 2 Volume blocks instead.  They essentially do the same thing, but there are 4 Volume blocks available (leaving 2 others for actual volume purposes) and it is much easier to set.  So please read the next section, but be ready to substitute Volume blocks for the Mixer blocks.  Also see this note at the end of this post about setting the Volume blocks correctly.
Starting with the electric row, I add 2 things to every patch: Mixer 1 and Gate/Exp 1.  The Mixer is responsible for splitting our Stereo Input 1 into the correct rows. Because the Mixer is in Column 1, please note that it acts a little differently than it normally would in any other column.  On Page 1, leave GAIN1 all the way up, but change BAL1 fully counter-clockwise.  (Gain and Balance 2-4 have no effect since the Mixer is in Column 1; that’s why the Mixer has to go first). This tells the row that you only want Input 1 Left to be sent to the rest of the row. Remember, our electric guitar is in the Front Input, which is Input 1 Left. On Page2, leave the Level at 0.0dB, but change the Output Mode to Mono.  We want only the left side of Input 1 to come into the electric row, but we want it sent to both sides of our Stereo Blocks and outputs.  If you don’t change this, you’ll only get sound from the left output.

The Gate is necessary as explained above, so set this as needed.  From here, you can add an Amp and Cab block, and anything else you would normally use in a patch. So by now you may have something that looks like this:

If you play the patch now, it won’t sound right. Even with only the electric guitar signal going, you’ll hear a dry guitar sound along with your effected row.  We’re not done!
On Row 1, add Mixer 2. Again only GAIN1 and BAL1 are functional since it is in the first column. Leave GAIN1 all the way up, but turn BAL1 fully clockwise.  This tells the row that you only want Input 1 Right to be sent to the rest of the row. On Page 2, leave Level where it is, and change Output Mode to Mono just as before.  Now you can add anything you want to the rest of the row for your 2nd guitar.

If you are using a setup like mine, you may want to add a Graphic EQ and Multi-Band Compressor after Mixer 2.  The EQ lets you shape your tone and the MBC helps control the full tone of an acoustic guitar.
I found it’s beneficial to have an Enhancer block in the acoustic row.  When you blend the 2 signals without the Enhancer, everything is coming right down the middle of the stereo field and it sounds a bit flat to me.  Frequencies start to clash and cancel out. With the Enhancer, the acoustic sound spreads out a bit, blending much better and keeping the full tone of each signal. Even at default settings, the Enhancer immediately improves the sound, but experiment with the Width setting till it sounds good to you.   I usually put this somewhere in the middle of the row.  Here is the full layout of my Clean Chorus/Acoustic Patch:

I sum the 2 rows at the end so they share a Filter block, which I use for a boost.  The 2 signals remain separate throughout the entire chain.
To help keep everything sync’d among my different patches, I use the Global Blocks feature new to the Axe-FX II.  I set everything in my acoustic row (Mixer 2, GEQ, MBC, Enhancer, Reverb) to a Global Block.  I want my acoustic sound to be the same on every single patch; it’s the electric sounds that change.  By using the Global Blocks, when I make a change to the GEQ on patch 4, the change will be saved to every other patch automatically. When I change to patch 2, the acoustic will sound exactly the same.  This was definitely a head-sore on the Standard and Ultra, but now it saves a lot of time and allows me to tweak my sounds more easily.
If your patch will always be using 2 separate guitars with a separate Amp block for each, you don’t need to use the Mixers. You can instead add an Amp block to Row 1 and another to Row 2 like normal, but then you must choose the appropriate Input on the ADV page of each Amp block.  Use Left for guitar 1 and Right for guitar 2.

You also need to select the correct input for Drive blocks on Page 3 of the edit menu.

But now you might ask why don’t’ I just use 2 Amp blocks instead of this Mixer mumbo-jumbo.  Well I DID use 2 Amp blocks for a while with my Axe-FX II, until Fractal Audio recently added the High Res Amp mode.  This mode turns on automatically when only 1 Amp block is used, and it returns to Normal Res when 2 Amp blocks are used in a patch. I tested this out, and I absolutely LOVE the High Res Amp mode, and knew I immediately had to get rid of Amp 2.  So like I said, my method is mostly for a single guitar with 2 outputs.  If they somehow get High Res Amp mode to work with 2 Amp blocks in a patch, I just might go back…
So there you have it: an updated method of using Mixers to use 2 guitars with one Axe-FX while using Copy Out1 to Out2.  I’ll have the patch available at the Fractal Audio Forum so you can download and have a starting point.

Stringer76 at the forum brought up a good point about using Volume blocks instead of Mixer blocks.  The Axe-FX offers 4 Volume blocks but only 2 Mixer blocks.  I never needed to use Mixer blocks for any of my normal patches, so I decided to use them to split the signal.  However, if you already use Mixer blocks in your patch, but have 2 spare Volume blocks, it’s actually easier to do.
Place Vol/Pan 1 in place of Mixer 1 above and hit Edit.  On Page 2, change the Input Select to Left Only.  Place Vol/Pan 2 in place of Mixer 2 above and hit edit.  On Page 2, change the Input Select to Right Only.

Left for Electric Guitar

Right for Acoustic Guitar

And that’s it! You have 2 more Volume blocks to use, and you have both Mixer blocks available for the crazy stuff in your head. I noticed no difference in tone, but the CPU usage is about .8 higher using Volume blocks vs Mixer blocks.  Shouldn’t be a deal breaker.