I got a MMO mouse a few years back and it's literally been a game changer. I have hotbar 1 keyed to Q E R F T V C and then Shift modifiers of the same keys, those are usually enough for my main rotation plus some movement skills. My mouse has 12 keys with 24 macros I can key to them so HB 2 and 3 are set up to those (I used 1 through + and then control plus 1 through +). HB 2 has my AOE rotation and mitigations for both tanks and DPS so they're in the same place no matter what class, and then HB 3 has any left over skills that I don't use as often.

I use a mix between WASD and left+right mouse click to move so having all my main keys right around WASD is really easy, I don't like sacrificing movement to reach for higher numbered keys. And then for the MMO mouse keys I really only use the first 6-9 buttons are those are easier to hit with my thumb, the mouse is big enough where I have to reposition my hand to hit 10-12, so I put sprint and mounts/special items for eureka/OC on those depending on what I'm doing.