I've given up on amp setups more times than I care to admit but can't get away from including tube amps in some form or fashion. I used to swear by a single Marshall half stack with zero effects which led to two half stacks with multiple floor effects. This eventually morphed into a stereo Rivera head accompanied by two Matchless 4x10 cabs. I have even tried out Guitar Rig with an external power amp and cabs. You lose all of your dynamic response in the virtual world. I have never really been satisfied with any of the modeling technology that has been available, and while I haven't actually tried the Axefx product, I always end up feeling like I have wasted my money when gambling on the new all-in-one solutions on the market. I guess that it really comes down to what you are trying to pull off and what you expect out of your rig. Lately I've been pretty happy with a combo duo but if you are stuck on the larger amps then you might consider a couple of 2x12's with a stereo tube head.