Good thread idea. I will tweak it a bit and go with non-obvious actors. For example, I agree that Joe Pesci was excellent in My Cousin Vinny, but he was an obvious actor for the role. Same with Tom Hanks and Forrest Gump (although I believe he wasn't the first choice for the role). I think Robert Downey was not an obvious choice for Iron Man, and I think that casting choice was really interesting, and ultimately successful.
Two that jump to the top of my mind:
Ricardo Montalban - Khan in Star Trek II. The Star Trek franchise wasn't even a franchise, and was on life support after a lackluster Star Trek - The Motion Picture. If II flopped, there wouldn't be a III, and the studio wasn't even sure they wanted to do II. It was a ballsy choice to bet the franchise on making a feature length sequel to a single episode that broadcast 14 years earlier, with the villain a B/C level TV star whose show was widely mocked. Montalban crushed the part, and started a franchise.
Courtney Love - The People vs. Larry Flynt. I know she was basically playing herself, but I thought Love was fantastic in this movie.