can anyone think of any?

I would say that Four Weddings and a Funeral was not ruined, but was great damaged by the casting of Andie MacDowell. It certainly turned what should have been a great British comedy into a merely good one.

The guy on the left.

Not miscast, he's just an all around shitty character.

And hardly the only serious flaw of the movie.

I find the question asked in the OP impossible.

Halle Berry in Catwoman

The movie was ruined when Tim Story was hired. The JA casting certainly didn't help things though.

Kirsten Dunst in Spider-man

Shameful that not one person has mentioned Sofia Coppola in The Godfather Part III.

I was so sure the first response in this thread would be a pic of her.

Kate Bosworth in Superman Returns. Totally miscast, and it really took me out of the movie.

Cyclops wasn't much better in that one.

Julia Roberts in Michael Collins.

Although it didn't ruin the movie by any definition, I've always hated Quentin Tarantino as Jimmie in Pulp Fiction - QT came off as a guy Jules and Vincent wouldn't even waste a bullet on.

Heather Graham, playing a prostitute with the finest teeth, in From Hell.

Mary McDonnell in "Dances with Wolves". She seemed about 10 yrs too old for the part she was playing.

Definitely High Fidelity, the chick who plays Laura, John Cusack's girlfriend. She's just awful. Ugly, no personality and not interesting. Sticks out like a sore thumb amongst that great cast.

And yet, Rob is supposed to be pining and heartbroken that they aren't together. I love that movie but she is the one huge downside to the film.

Tony Soprano in "Where the Wild Things Are"
Took me out of the movie every time he opened his mouth.

The offspring of Clint Eastwood and a grizzly bear as Batman's voice in The Dark Knight.

now that's just silly.

Sofia Coppola in The Godfather Part 3. The role was originally intended for Winona Ryder, who would probably have been better but still wouldn't have seemed quite right as Michael Corleone's daughter. Coppola was just atrocious in the role, though, which, being a pivotal role in the film, dragged the whole film down.