The first thing to know is that you will never bind an in-combat key out of one hand's easy reach from WASD. Below is a picture of the most useful keys for in-combat bindings.
Of course, if you have large hands, feel free to add more keys on the right, but the goal is to always have your hand hovering over the movement keys. If you need to stretch your hand uncomfortably to reach something, it is not important enough to use in combat.
I find that QERTY make the best rotation keys, and 1-4 the best sequence-breakers. We will cover these later, but for now know that a rotation is a string of abilities you repeat over and over to maximize your output, and a sequence-breaker is an ability you opt for in certain situations to improve your rotation. I also find that 6, T, F and G are good for abilities you use once or twice a minute, such as short-term buffs, while TAB and ~ are great for "big gun" abilities that require some commitment. Meanwhile, the fingers curl back for ZXCV, so these make great defensive keys, with B as a last-ditch panic button. F1-4 are good for targeting your party for buffs, or for camera angles, or /Yelling all manner of big important warning.
The modifiers, SHIFT, ALT and CTRL, are not just there to allow you to use more abilities, they are to keep you from using certain abilities at the wrong time! So a hunter can set her pet's abilities to SHIFT and QERTY, but warrior stance-switching, paladin Divine Intervention, and rogue Vanishing should never happen with just a simple keystroke. Auto-run needs to be a twofer. So many wipes could have been avoided if people had to commit to dundering forward blindly. Remember, every action you can use in combat needs a key, but the the more motion necessary for an ability, the less often you use it.
Some hints: Experiment to find the layout that works best for you. Turn off all your combat bars and try memorizing abilities by touch (this is not a good idea permanently, as you still need to see cool-downs.) Trust me when I tell you to make a list of your in-combat key-binds, in case they ever get erased from the game.
Finally, you do not need to keybind everything. Vanity pets, mounts, trade skills, out-of-combat consumables like food and elixirs, all of these can stay on a pretty bar for your clicking amusement. Certainly, none of these need to be bound to any of the keys in the picture, unless poor ALT needs something to do. Me personally, I use the number pad for consumables and the arrow keys for gear changes (most outfitter mods have a key-binding option.) For these sorts of things, key-binding is a personal preference, but for combat, it is a must. No matter how fast you mouse-click, with practice, keys will make you even faster. And our goal, again, is to feed a calculator big numbers as fast as we can.
Wuh-oh! Did I just say numbers? No more putting it off, readers mine. Tune in next time to meet Milo's good friend, the Mathemagician.
(Also tune in tomorrow for my first-ever irregular "Aside.")

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