I gave up on guitar amps in (believe it or not) 1968, and started using FRFR keyboard amps that were made by RMI. (Admittedly, this was because I created effects to give me the sound I wanted before hitting the amp, so the amp sound became less relevant.) At the time, tubes were getting inconsistent in terms of quality, and because I was playing over 250 dates a year, reliability was also an issue. I continued to use FRFR, and switched over to the Bose L1 when it came out because it could also feed FOH, and the line array was great for feedback by holding the guitar parallel to the speakers. On gigs with DJs in Europe, I didn't use any amp - just fed the AdrenaLinn output into the FOH, and got feedback by touching the headstock to the monitor speakers.
The only time I use physical amps any more is in the studio to get a specific tube amp sound, because of the miking options that are possible with a room and cabinet. But this is maybe 1% of the time. Helix Native and other amp sims are a) all I really need, and b) can get sounds that are difficult or impossible to obtain with conventional amps. If I had to use physical amps and crossovers to do my multiband presets, I'd go insane. And broke. Or both :)
I do find that amps have a certain kind of "feel" when playing live, which I believe has a lot to do with the room but also, a speaker cabinet is a very complex filter. So I think the comments about using Helix with a cab are spot on when you want that amp "feel."