I usually drive from the guy that gets aggro. In WoW/Rift/etc. it's the tank, and in EVE Online it's the first (usually) guy I warp into a mission. I usually do this because positioning of a boss or a room-full of aggro is easier than targeting/assisting with the alts, even the healer/salvager.

EVE is a little bit different, as I have 5 guys capable of tanking, and ISBoxer makes it pretty transparent regarding which one I'm driving.