Cataclysm killed off Cairne Bloodhoof and apparently Magni Bronzebeard (I'm still hoping that one can be reversed!). Before that, we (apparently) killed off Kael'thas, the Blood Elf leader, and Zul'jin, one of the Troll leaders. Heck, Fandral Staghelm, while not exactly a leader, was just killed off in 4.2. Blizzard isn't afraid to kill off its own creations, so who do you think Blizz will kill off in the future?

I'm sure Magatha Grimtotem is up next. Revenge is sort of a theme we got going on in WoW, and I doubt that old meatloaf-to-be will be useful in the next expansions as anything other than a raid boss. But she can't be the only one.
Personally, I'm betting on Sylvanas. Something big is brewing, and despite the fan hate of Garrosh, I have a severe doubt Metzen will let us off the hook on that guy any time soon. The Undead are going to need to be brought further into the Horde, and unless we're getting a third faction (/pray), I'd be we'll be finally putting that Undead to rest.

Who else do you think will be going the way of Cairne? Will the death knights' leader, serving no known purpose, get the axe next? Will Thrall perhaps die for real? Or will someone bump off the cheese master?