My hot bars were pretty haphazard. Initially they were based around the numpad, but as I grew more efficient, some of the more frequently used abilities were moved to mouse or modified-mouse (e.g. alt, ctrl) buttons. Primary filler nuke was mouse4 which was easily and simply accessible by my thumb, heals on my druid were various modified-mouse buttons because I was using Clique and Grid, shaved much time off healing if I didn't actually have to click-target people. Ground targeted effects like Rain of Fire, Shadowfury on the mouse for quick click-and-target. Ctrl/alt/shift/etc space was also an important key. Major damage skills that had cooldowns (like haunt or DoTs) were on 1-4 of the number (though also bound to numpad, but more accessible with left hand). Toggle melee auto attack was z. Major cooldowns were on modified/numpad minus/plus/enter (could modifier with the left hand and thumb the numpad keys with the right).
Like I said, very haphazard and organic, but it basically worked out that I pretty much always a hand on WASD and the mouse so I could easily move around, look around, and (in particular, while holding mouse 2) strafe. A very big part of maximizing your output, whether as damage or a healer, is to Always Be Casting, which means taking advantage of very small windows in the GCD (such as after an instant) to reposition yourself in advance of what's coming (and also knowing when you don't need to move at all). When I was a tree I could basically just waddle around casting, it was hilarious and fun, and I hated losing that when they nerfed healers in Cataclysm (even if I understand why they did it).