I think the main problem are for the keyboard and (typical) mouse users. Typically, you move with wasd, and your keyboard hand can't move around too much, so trying to use the entire hotbar(s) of all 12 buttons + ctrl/shift/alt gets very hard/awkward. It's not like you're playing a piano here. You can try to rebind keyboard buttons so the hotbars aren't 1 through = buttons, and more situated around wasd keys, but many people try to use the default setup.

One way people work around this is they typically have the most important skills set to 1-5ish and ctrl/shift/alt 1-5, and the other hotbar buttons they either mouse click or physically move their hand (which can be bad if the fight requires movement at that point). But some jobs this doesn't work well as they have too many important/commonly used abilities for that trick to work comfortably.

For MMO mouse users (people with 6~12 buttons on their mouse) or controller users, this is not an issue. They'll have easy access to dozens of hotbar button presses while still comfortably having access to their character movement.