The thing ab high-gain is that pure cab clearly changes the frequency response, and if you want the same djent and punch and fizz you cant just set it and forget it. You need to eq a bit afterwards sometimes.
I hear the 8-bit thing that DL is talking about. And i agreed 100% at first. But after setting it and trying lots of rigs, i felt like the sounds i was getting sounded like an amp in the room, not digital processing on top of a mic'ed cab. Switching on/off, the most obvious change is in the highs, and it can often sounds kind of fake. But switching back to pure cab off, you can hear all the noisiness and phasing and crap that comes along with micing. Pure cab def has more "body" but seems to have less character. I havent tried yet but i wonder how tweaking the cabs Character param sounds with pure cab on.
Im not trying to defend pure cab. There are several rigs i a/b'ed where pure cab off was clearly preferable. On the whole i think its great. But a per rig setting will be great.
Some of you may like a phasy sound. Pure cab seems designed to eliminate that, so if thats your thing you are going to want to keep it off.