Why not use a combination?
I have Clique (since it works on all frames unlike alternatives that include raidframes) and have a lot of macros in it (using @mouseovertarget etc..) as well as using its otpions to differentiate between friend and foe, in and out of combat.
I also have some spells in my bars just to have a place where their CD shows should I get distracted.
And then there are my macros in some real accessible places (mouse buttons 4 and 5, mouse wheel, Q, E), on those I mainly use modifiers to choose spells and predefined targets (target, targettarget, focus, self), there are 27 possible combinations after all (26 for mouse wheel up, CTRL+SHIF+ALT wont work for that one).
Those I can use while moving and moving the camera, without running around the whole keyboard. I almost never get caught having to cast a spell I cannot access while having to move a the same time.
While I could use clique to cast on my focus target, I'm just to lazy to move my mouse for most of those spells.