- Joaquin Phoenix, Signs, 2002. Mark quit when diagnosed with a brain tumor (benign), also referred to as a cyst in his inner ear. After surgery, he suffered a partial facial paralysis. M Night Shyamalan kept Phoenix for his next feature, The Village, 2004. The cyst was more fun.
- John Turturro, Fear X, Denmark-UK-Canada, 2003. Also seen: Ray Liotta, Gary Oldman, Tom Sizemore.
- Michael Vartan, Monster-in-Law, 2005. He was not interested in welcoming Jane Fonda back to movies after 15 years away. Hence a break for the Alias TV star.
- Daniel Craig, Infamous, 2005. In a second film within a year about Truman Capote. Nark Wahlberg was originally attached to play Perry Smith, replaced three months later by Ruffalo until he dropped out as well. to allow another rough trade role for Craig... the new 007.
- Edward Norton, The Incredible Hulk, 2007. Welcome to Hollywood, Louis Leterrier. “I actually wanted to cast Mark as Hulk and Marvel was like "No, you should get Edward Norton because he's more famous…. Ruffalo just does smart, intellectual movies But that's how I know him,” the French cinéaste told The Huffington Post’s Mike Ryan. “We’ve stayed in touch and it's why he said "absolutely" when I offered him the part in Now You See Me, I was thrilled to meet and work with Edward. He’s a great friend… we really do love each other! But the first half of the movie is really mine and the second half is the studio's expected Hulk movie - two giants kicking each other’s ass.” Ruffalo later played Hulk in The Avengers. When people are asking Leterrier who's the better Bruce Banner, he’s ultra diplomatic. “Both are great, both are fantastic.”
- Ben Stiller, Greenburg, 2008. Quit auteur Noah Baumbach’s independent drama days after the homicide of his younger brother, Scott.
- Joseph Gordon-Levitt, The Dark Knight Rises, 2011.
- Ben Mendelsohn, Killing Them Softly, 2011. As the title changed - although Killing Them Softly IS Cogan’s Trade! - so did the ex-con robber from Ruffalo to Javier Bardem or Sam Rockwell in the testosterone-packed film (really) noir. Changing George Higgins’ 1974 Boston-set thriller to New Orleans in 2008, made it more suitable for “enforcer” Brad Pitt’s line: “The United States is not a country. The United States is a business. Now gimme my money.”