The Neon Demon and Dracula are two of my all time favorite movies, but he's only got a small part in the former and is pretty bad (hilariously, endearingly so, though) in the latter.
I'm gonna go with Speed. But the answer could easily be Point Break, The Matrix, A Scanner Darkly, or John Wick on a different day.
Like others have said, he's had a fantastic career.
I was also really impressed with his performance in Sam Raimi's underrated The Gift. He's good at playing abusive assholes, although fortunately that's not the kind of role he's known for.
EDIT: Glad to see Constantine's getting a lot of love in this thread!