Personally, when I first got my AFX, I was hoping that I could just run it into my 2x12 G12M cab and hear pure heaven... well, that wasn't quite the case, sadly. I tried everything I could, but I could never get the Axe to sound decent through my guitar cab, to be honest. I began running it through my Yamaha H50's in my studio and I was becoming quite happy with the sound I was hearing, which led me to do alot more research on this topic and figured that FRFR was the way for me to try. I also decided on this route due to the fact that I had just spent alot of $$ on this "magic black box" and by going into a "colored" guitar cab, I realized that I would be wasting all the cabs, mics and custom IR potential that the AFX offered, as I would be turning those things off generally when running into a typical guitar cab.
Now I haven't tried the Matrix NL cabs or anything, but I did have Mick at Xitone build me a custom 1x12 FRFR cab for this thing and so far I'm very happy with the results, even though I'm still searching for my tone and learning the ins/outs of the AFX. By powering it with a Matrix GT1000, I do feel that it does come very close to the "guitar amp" feel for me, but some say they don't get that result and would rather play through a typical guitar cab. In time, I'd like to try the new Matrix cabs and hear/feel the differences and compare, but can't really afford that venture at the moment. But as of now, my Xitone has been giving me a great tone and will be what I'm building all my presents around for now, with no regrets on my decision to go FRFR with my current rig.