My wife and I have been discussing this very topic, as lately I have gotten really excited about recording with Amplitube. Mind you, I have a studio (double-wall construction, double drywall of different thicknesses on channel, acoustically treated, etc.) and I have been collecting really high quality gear over the years. I also have my amps mic'd up at all times. Add that to the fact I've been known to be a tone snob and well, you can see her consternation. She thinks I am going back on my principles, and in some way I don't yet understand that I am "cheating". Look, running my ES335 through a Skreddy pedal into a real Echoplex then through a first edition Small Stone phaser (hence my forum name) and then split using a TC Electronics Stereo Chorus pedal into a 1964 Super Reverb and a modern Dr. Z Amp gives my a sound that I cannot exactly duplicate in the software. However, just try to come back a week later and recreate some crazy sound - especially with a few analog modulation devices in there.
While Amplitube is not 100%, it seems that if you tweak it a bit and mix it well with the rest of a project, you're hard pressed to hear the difference. You can tell, but you have to go looking for it, if you know what I mean. I love that I can record a part, and then go back and try different amps, and more importantly, different effects. Being able to play with multiple delay units on a looped guitar part to find just that right sound, and have perfect recollection of it later - very cool.
Maybe I'm fooling myself and I'll jump back over to the amps with even more snobbery - who knows? :)
Something I found that helped when using Amplitube. I run into a Valvulator running a 12AT7 tube in it so I can push through lots of effects without signal loss (tone snob, remember?). The Valvulator has two outs, and I've found if I plug the guitar into the Valvulator and the Valvulator into the input on my interface, I get a better tone and response than plugging directly into the interface. As with pedals, I think the Valvulator keeps a nice consistent load on the pickups of the guitar, and pushes out a good consistent signal...