Here's exactly how I do it, which works just the way it should. I can live re-amp the signal while the track is playing and tweak the Axe-Fx in the mix. Note that I do not use the USB for this, and that I'm not in any saying that this is the best way to do it - it's just how I go about it.
I'm using Reaper 64/OSX and a MOTU 828mkii.
Cabling is pretty simple. I record my rhythms mono, but the same applies for stereo, so everywhere I note one connection, make it two.
Guitar -> Axe-Fx II Front Input
Interface Output 1 -> Axe-Fx II Rear Input
Interface Main Output -> Monitors
Reaper Main Output -> Interface Main Output
Axe-II Output 1 -> Interface Input 1/2
Axe-II Output 2 -> Interface Input 3/4
There's nothing special/unusual there other than that I run an extra output from the interface into the back of the Axe-Fx.
I setup my presets like this, so that my regular tone goes stereo out of Output 1, and the DI goes stereo out of Output 2 via the FXL block.
Then in Reaper, I record a regular processed track by arming the track with the input on Input 1/2 (which I have named "Axe-Fx Wet") and a second track with the input set to Input 3/4 ("Axe-Fx Dry"). You can name your inputs in Reaper in the Audio preferences, and most DAWs have the same functionality.
Then, when recording, I just keep the OUTPUT level on my DI track all the way down (so I don't hear it when I'm riffing away). It's still recording, it's just not monitoring.
What I end up with is a clean DI and a wet tone for each track.
Once you have your DI track, set the OUTPUT of the DI track in Reaper to the hardware output that routes to the REAR input of the Axe-Fx. In this case, Analog 1 is Output 1 of my MOTU, and that's cabled to the back of the Axe-Fx.
Make sure that Master/Parent send is unchecked, and that the hardware output is the only output on that track, so that you don't hear the DI track at all when you play it back - the only place you want it to actually go is to the Axe-Fx.
Now, on the Axe-Fx, go to I/O -> Audio Tab and set Input 1 Left Select to Rear. If you just run your DI out of your interface to the front of the Axe-Fx, obviously this isn't necessary, but I don't like to swap cables around and there's a bunch of shit in front of it my chain. Plus, I'm lazy.
So all you're doing here is taking the DI that you created in Reaper and sending it to a new output on your interface that's cabled to a different input on the Axe-Fx. Easy as that.
Now just create another track for your reamped signal, and have it use the same inputs that your regular tracks use. So if Output 1 of the Fractal is the output that you use for your wet signal, your reamp track should use that for the input.
Then just arm the track, mute your original wet recording and go to town. You'll be able to live re-amp with the Fractal while hearing the rest of your mix in context.
Here's a video of it in action: