One problem, at least in a live rig, is the speakers. I don't care what sort of EQ the modeller applies, you can't get an open back combo speaker to sound exactly like a 4x12 closed back, or vice versa -- to my ears, Line6 etc. are not even close. Even if the modeller does a perfect job of emulating dozens of tube amps, this (and transformer - speaker interaction) means that you will still need a half dozen or more speaker cabs in a live rig for multiple convincing tones.