Sometimes, fate works against a director's vision. Often, this hurts the film. In this case, though, fate worked in its favor. Henry Fonda wasn't available, nor was Charles Bronson, so instead of those iconic actors we have Clint Eastwood as Blondie and Lee Van Cleef as Angel Eyes, and I couldn't imagine it any other way.
Eastwood is a perfect actor for Leone's extreme close-ups. He acts with his eyes in a way few actors are capable. Clint's now famous squint lends itself perfectly to Leone's style and vision. In a film that puts so little emphasis on dialogue, the action becomes all the more eloquent. Eastwood's way of moving his eyes, squinting or relaxing his squint, looking or not looking at someone, speaks far more than his words do.