The biggest problem with clicking abilities, in my experience, is movement. Turning and moving with the keyboard just isn't quick enough. Particularly turning.
Back in Wrath, I got chewed out by my raid leader for keyboard turning, which I had to as a result of clicking my abilities. So, I took up a radical solution; I completely unbound movement from my keyboard, and did all movement with the mouse (it has two side buttons, one for autorunning and one for backpedaling). To this day, I have QWER, ASDF, ZXCV (all with shift/control modifiers as well) and 1-5 as ability binds, with virtually every single class ability I have (including niche ones) bound; I currently play a Frost DK, and the only abilities from my spellbook that aren't bound are Blood Strike (provided I even have it anymore, I haven't checked) Icy Touch, Blood Boil and Death Gate (I click that). My engineering enchants, potions, trinkets and anything else that I would use in a fight are also bound.
The only disadvantage is that the mouse-movement solution that I use doesn't provide for strafing. That's not really an issue as melee, and when playing ranged I substitute strafing with jumping and turning midair. It works about as well and satiates my melee-driven jumping addiction, but that might bother some people - though they could still bind it somewhere if they wanted.