Cluster your hotkeys so that the most used are in the most convenient spots for you. I like to keep my defensive/healing macros together above my offensive ones.
I have my potions and a few utility macros on my number keys.
Qwerty keys are healing and buff spells
asdfgh are all offensive spells
zxcvbb offensive spells/debuffs
Keys left over on the right are more utility spells/actions
Spacebar usually commit to my most used or important action.
Thats just my setup not sure if it's the most efficient but works for me.