I think to make this list you have to be a top 5 pick.
Remember the big discussion when Leaf came out was Leaf or Manning?
Leaf is the CLEAR #1 pick in this list for the biggest bust.
Tim Couch took a team to the playoffs, but was battered over 3 seasons, and I suspect we'll see him in an NFL uniform again, he's still young, and if his elbow/shoulder have healed after both have been operated on, he's at least backup caliber - still, he did 1000 times better as a pro than Leaf did.
Tony Mandarich actually had a decent career after he came back to the game - he was clearly roided up big time - he and Steve Emtman, a DT from Washington, where 2 guys who were animals in college because they were roided up as much as anyone I've ever seen.
Charles Rodgers broke his collarbone twice, and I think he's just plain tentative now.
Ricky Williams may be an idiot, but he was a damn good running back. Coach Ditka made a terrible trade at the time, but he was hardly a bust.
Rex Grossman is a starting NFL QB, and his team is what, 9-2? Way too early to be calling him a bust.
Heath Shuler - bust. Cade McCown - bust, Andre Ware, bust, David Klingler - Bust - Akili Smith - Big time bust - Courtney Brown - injured too often to ever really contribute - bust.
Mario Williams is solid - he's getting bad pub in Houston because they passed on Bush, but he's a cornerstone DE as long as he stay healthy.