This is kind of a difficult question. Do you mean what film an actor was in that made them popular or maybe when they finally sort of hit a homerun at their craft?

My personal vote would be Pulp Fiction for Jon Travolta; the film turned him from a b-rated joke into a legitimate star again.

Sin City put Micky Rourke back on the map, and The Wrestler legitimized him as a serious actor.

However, I think we often give actors and actresses too much credit. Great scripts and great Directors often play a much more pivotal role in what an actor can accomplish.

In the Shawshank Redemption we undoubtedly see Morgan Freeman and Tim Robbin's best performances of their respective careers. Morgan Freeman also had Driving Ms Daisy, but to be honest I haven't seen any work of real substance from either of those actors since.

Hayden Christiansen was praised for his breakout performance in Life as a House and Natalie Portman has received tons of praise for Black Swan, but look at their rather underwhelming performances in the Star Wars prequels.

I also agree with the Jim Carrey example in another comment for Eternal Sunshine, but again you are dealing with Michael Gondry. I think it will be a very rare thing to find an amazing performance from an unsuspecting actor without the back up of a solid script and or director.