Cruise could have been great as Stark, but the tone of the movie would probably have been very different. Probably more intense, less funny.
A related post from the Simplies -
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I think that as much as they'd hate to admit it, the Marvel movies have worked in large part because of the casting. Robert Downey Jr. pretty much owns Tony Stark, at this point, and both Thor and Captain America have flaws as films that are overcome because of the excellent performances by Hemsworth and Evans. Their performances, I think, are the gateway for non-genre fans to buy into the films. Avengers is the film that works the best, overall, but even there I think a part of what made that version of the Hulk so successful was Ruffalo, whose Banner was far more engaging than Norton's or Bana's.
Thinking about it, if and when Marvel has to recast the big three, they're going to need to find people who bring their own thing to the role, or go the legacy route. Iron Man's the easiest, where you could simply have Stark show up long enough to pass the torch on to Rhodey. For Cap, depending on what they do with Winter Soldier, they could hand off to him. Thor's tougher, but they could just let that end with a trilogy and move on to other characters.
