The size and weight, mostly. A Mesa Road King II is as heavy as a head as most combo amps are. Then add in a ATA case, and a 2x12 or 4x12 in a case, pedal board and, you guessed it, case. Loved the sound most times, as versatile as a single amp could be. But the weight... and did I mention how heavy that beast was? Brutally heavy.
I still have tube amps, but they are for using at home when the mood strikes. If the gig requires movement, it's the two small cases, a monitor, a stand, guitars. All fits in the back seat of most cars. Lighter (let's face it, ATA racks or cases are heavy empty) and much smaller.
Sounds great, less filling.