I use E-S-D-F for movement, and everything else in the zone bounded by Q-I-,-Z for hotbars. I also add to that the number keys 1 through 8. That gives me a rectangle with four rows of eight keys each. It can be a little bit tight to get everything you need for combat in, depending on the class, but it can be done.

I arrange my hotbars on screen into the same visual pattern; four hotbars, eight slots each, in a grid mirroring the keyboard layout. I leave the slots that correspond to E-S-D-F blank, bind the keys in the same location that matches their location on the keyboard, and the just drop my spells onto the grid until it's filled.

My most used combat abilities (basically the stuff in Core Abilities tab) go on Q-W-R-T-Y and A. I always put my stun break on G, major self-heal or health pot on H, interrupt on J, and potion macro on K. (I also have a side mouse button on my Logitech G400 bound so that it produces a J keypress instead of a mouse button click.)

I try to keep things zoned roughly by some sort of theme; so the bottom row Z-, is all my cooldowns, with the shortest on the left and longest on the right. Number keys are all my ranged and control abilities, with some miscellaneous macros and junk at the right end. The core Q-Y+A zone is my primary combat rotation. G-H-J are always "oh shit" keys.

As I get used to a new spec, I just drag stuff around in the grid according to how much I am reaching for it. Things I use more gravitate toward the Q-W-R-T-A hotzone, and other things migrate to the outer reaches of the grid or the number keys and Z-,.

The visual mirroring from screen to keyboard helps out a lot when learning a new class or swapping between classes, because if I forget where things are I just look at the hotbars, and I instantly know where to reach for what I need, without looking at the keyboard.

I basically have no other keybinds but these. I bound my entire number pad to open all of the UI windows like character, map, friends, etc., so I could take the "microbar" off the screen.

For everything else like buffs, raid macros, target and world markers, trade skills, hearthstone, portals, etc., I use OPie. It is brilliant. My OPie rings all are bound to the F1-F6 keys, which I mirror to the G1-G6 special keys on my Logitech G105.