How about Marlee Matlin in Children Of A Lesser God?
The almost too bare-naked dysfunctional dynamic between man and wife would be near impossible to replicate with anyone but Richard Burton and Elizabeth Taylor in, Who’s Afraid of Virginia Woolf. I can’t think of anyone who could have replaced Sandy Dennis, either. What absorption into character for the whole cast! Painful to watch, but brilliant.
More in line with the spirit of the OP, I don’t think most of the cast of Dr. Horrible’s Sing-Along Blog could have been anyone else. Not because only they could pull it off, but rather because the film/series was concocted under the circumstances of the writer’s guild strike. The cast is largely made up of Whedon’s friends, and was largely thought up and written by the cast and crew in response to said strike. It was simply made under different circumstances than the traditional audition/cast cycle.
For that reason, while I’m sure the roles could have been shuffled around, or maybe you could argue that Whedon could have gotten a different set of friends and colleagues for the parts, the circumstances under which the entire thing was done presented a relatively unique challenge that made the cast what it was.
Similarly with Whedon’s Much Ado About Nothing. Obviously plenty of other people can play Shakespeare characters, but the whole thing was basically just a goofy excuse by Whedon to shoot a Shakespeare production in his house during his vacation. The actors he chose, he picked because they were his friends who would be interested in chilling out and shooting an artsy Shakespeare adaptation.
Or as Phil Connors in Groundhog Day.
Michael Keaton.
I’m not seeing it.
Well, pick a line: eyes go wide, he says “Ned?!?” and slugs the guy: sure. Delivering the “I’m a god . . . I’m not the God . . . I don’t think” bit: yep. Replying with offbeat sincerity that his dad was a piano mover, as if that explained everything: easy.
I can see him tilting his head as Doris-asking-for-a-roll-of-quarters while timing his walk to the back of the armored car – or doing that broadcast for the nth time, and starting to drone through the scripted remarks. What can’t you see him doing?
N-n-n-no. Still not seein’ it.
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Anyway, as the OP has explained, for a movie of that size you need a big name to draw people in who would otherwise maybe not have gone to see it. Colm Wilkinson isn’t going to do that, nor are any of the hundreds of Valjeans who have played the part all over the world. Hugh Jackman can.
But that’s not really an issue of being able to play the role, it’s simply an issue of marketing. That’s rather different than cases in which an actor was especially suited to the role itself.
Brian Cox and Mads Mikkelsen have also been fantastic as Dr. Lecter as well.
Two that jump out to me are Bill Murray quite literally playing himself in Zombieland and Kareem Abdul Jabbar playing Roger Murdoch in Airplane.
He may be crazy now but Gary Busey as Buddy Holly, he just seemed to live inside that role for a while. He brought this kind of genuineness to the role, he lost a lot of weight to fit the part, and he really sang the songs and played the guitar parts. I’m not sure if he captured how Buddy Holly was in private moments, but he seemed to nail his persona.
As usual, I agree with my friend silenus. No one could have replaced Gregory Peck as Atticus Finch.
My entry: Robert Preston as Professor Harold Hill.
From IMDB:
I can just imagine Sinatra trying that role. It would have been awful. Cary Grant would have been even worse.
Matthew Broderick was terrible too.
Pshaw! Pauli Shore would play a spot on modern Atticus Finch.
I would nominate Laverne Cox in Orange as the New Black. I envision a casting call: Wanted, sexy transgender black female who can act, with nonTG twin brother who can also act to play her pre-transition.
Jane Horrocks in Little Voice. Can’t really imagine anyone better to play the Michael Caine part in that movie either, but definitely Jane as the thing was written for her.
Oh man, there was another one, I JUST had it.:smack:
ETA: Guy who played Tevya in Fiddler on the Roof, play & movie. I guess others have done the role in times since.
When the movie first came out, I read a review that said Val Kilmer was a horrible actor and it was sign of what an unoriginal, cliche character Jim Morrison was that even a no-talent like Kilmer could portray Morrison so accurately.
That was such a breathtakingly illogical statement that I’ve never forgotten it.
I saw Cary Grant in 1985 in one of his “An Evening with Cary Grant” shows, where he would appear on stage somewhere, and after a montage of clips from his movies he’d come out and sit on a stool and answer questions from the audience. Someone asked if he’d considered doing My Fair Lady and he said that he told the producers that he not only wouldn’t do the movie but if they didn’t cast Julie Andrews as Eliza Doolittle he wouldn’t even see it. 
On preview I happened upon longhair75’s post which says that IMDB says Grant made the same comment in regard to Robert Preston and The Music Man. I don’t know whether Grant made a habit of making this kind of quip or whether the writers at IMDB got their actors and movies mixed up, but I do that that his remark about Julie Andrews is accurate because it came straight from Grant himself.
Inarguably, only Mike Myers could be Austin Powers, since he created the character.
Or, you know, Michael Caine.
Tom Cruise disagrees.