My setup is largely determined by the team I am playing against, and whether I or my opponent starts with the ball. If I am against a speedy team, like elves or rats, I always keep two guys deep, even on offense, because if they somehow get the ball they can set up a quick score if you don't have any safeties. Against beefy teams I tend to keep my guys off the line, forcing them to move in to me, and allowing only a few "free hits" before they must blitz.
I try bully the shit out of speedy teams by trying to knock guys to the sidelines and pinning them there when possible. I play as Chaos a lot.