I can think of several:
Sofia Coppola in The Godfather III. She replaced Wynonna Ryder who had some mental issues during filming. Coppola was so bad she almost ruined an otherwise mediocre movie.
John Travolta as a WWII Army General in The Thin Red Line. Granted, it was a small part, but he just came off as John Travolta trying to play a general.
Don Rickles as a Casino Manager in Casino. Please. The love affair between Joe Pesci and Sharon Stone was downright gross and farfetched.
Emile Hirsch as the alpha dog drug dealer in Alpha Dog. He seemed more like just a little weasel and not exactly as tough or intimidating as his character called for.
OJ Simpson as an astronaut in Capricorn One. LOL!
John Malkovich as the terrifying Confederate bandit in Jonah Hex. WTF?