Mark Ruffalo is this to Edward Norton as Bruce Banner in the Avengers movie.
Don Cheadle replaced Terrence Howard as James Rhodes.
Howard Stark has been played by a different actor in each film he's appeared in (Iron Man, Iron Man 2, and Captain America). Somewhat justified on that last one, as Howard Stark was supposed to be about 20 years younger than he was in the Iron Man movies.
Zachary Levi replaced Joshua Dallas as Fandral thanks to his commitments to Once Upon a Time which is a reversal of The Other Marty, as Zachary Levi was originally cast as Fandral in Thor but couldn't because of Chuck related scheduling conflicts.
Josh Brolin portrays Thanos from Guardians of the Galaxy onwards, after Damon Poitier made a brief cameo at the end of The Avengers.
Anthony Mackie says he wanted to play the Falcon to show the kids in his family (as well as black kids in general) that black people can be superheroes too. In general, he's been very vocal about the need for greater diversity in superhero movies.
Michael Douglas says this was his major motivation for playing Henry Pym in Ant-Man. He even took his son to Comic-Con to promote the movie!
Trolling Creator: It's been tradition since the first Iron Man to have a post-credits scene. Leading up to The Avengers, these scenes foreshadowed events that would be touched on in other films. Starting with The Avengers and continuing on in Iron Man 3, Thor 2 and Guardians of the Galaxy, these foreshadowing scenes are played mid-credits, and audiences who are Genre Savvy enough to wait to the end of the credits are rewarded with a pointless, humorous Brick Joke for their patience.
A Runaways movie got as far as casting calls before they realized that it's just too complicated a mythology to dump into the franchise all at once (in the comics the plot ropes in time-travellers, mad scientists, aliens, crimelords, witches, mutants and pan-dimensional god-monsters, and that's just the origin), particularly before they'd even got the Avengers fully established. Of course now that they're brave enough to make something as obscure and bonkers as Guardians of the Galaxy it's safe to put it back on the "coming soon, maybe" pile.
The Wasp was initially going to be part of the team in The Avengers, and was even included in earlier drafts of the script. Joss Whedon is on record saying that he really enjoyed writing her, but ultimately had to cut her out of the script due to there being too many characters.
It now seems like Janet will not be in film - according to Michael Douglas, Janet dies while making the first Ant Man.
Emily Blunt was Marvel's first choice to play Black Widow, but she had to drop out because the filming conflicted with Gulliver's Travels which she was contractually obligated to.
And now, Edgar Wright's Ant-Man, which could well have been one of the most individualistic visions within the MCU.
Early drafts of Guardians of the Galaxy had Nova as a central character. He was cut because they felt his character arc was too similar to that of Star-Lord, and because James Gunn does not like the character.