As I alluded to, the best setup I've had was Fryette Powerstation 100watt, Axe FX III, and my 4x12 Egnater cab. For live usage, I'd need to add my FC-12 into the mix, and probably a couple of extra expression pedals for wah and volume and all that.
But the rig would honestly be no more lighter or convenient than using a real amp head, to be honest. The only advantage it really gives is being able to do much more complex patches and signal routing, and would easily lead me down a rabbit hole of not writing songs, and just doing clever-dick shit for the sake of it.
I'm pretty comfortable with my Mark V and some pedals at this point. Axe III for home use.