After reading everyone's input, plus my own opinions, here are my top 5 (along with their best role):
1) Leo - The Departed
2) Hanks - Forrest Gump
3) De Niro - Goodfellas
4) Cruise - Jerry Maguire
5) Philip Seymour Hoffman - M.I. 3 (haters will bash this one I know, my only response is any role he plays, he is fucking domination in it. He can play a nerd or a bad ass, and both will be pulled off with excellence.)
Just missed list: Brad Pitt- Troy, Matt Damon- Good Will Hunting
My next list will be top 5 single performances in a movie.