I have the skull bound to a mouse button.
One side button is skull or shift-click for X, the other is Ventrilo push-to-talk.
It makes 5-mans really smooth because I can mark up a skull so quickly, the DPS see it before I engage. This can help if you’re tanking in Blood spec and want to establish threat with its weaker AOE. DPSers generally follow markings.
I need a new fancy gaming mouse, will get one eventually, but for now I use this really old crappy one with two side buttons.
Keybinding in general is further discussed over here.