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Jimmy Stewart as George Bailey
A lot of actors do a great job, but in the end are replaceable. The character would have certainly been a little different, but you would still have the story and a few new wrinkles. I really think Jimmy Stewart is irreplaceable as George Bailey. It's not only the every-man, good hearted nature. It's the mental breakdown he goes through. Considering Stewart's very real war experiences it's entirely likely we are watching someone with PTSD on film, and at a time where that wasn't something to show or discuss.
Alan Rickman as Hans Gruber is so great too.
I'll add in George C. Scott as Patton. I think the bio pic is especially difficult to cast. While fictional characters are open to interpretation, you can't cast a bio pic without the audience doing a comparison to the original. Not only on the physical side, but also the character.
Finally, on the other side of the coin when it comes to playing real people is Jason Issacs in The Death of Stalin playing Zhukov. From the moment he comes on screen, you know you are watching a fictionalized caricature but it's absolutely riveting. I don't know if that is just a great script or if Issacs added the right mix.
