1. Farley Granger in Strangers on a Train
Granger wrecks every Hitchcock film he's in (he's awful in Rope as well), and in this one, Robert Walker's silky pyschopath runs rings around his quavering, ineffectual tennis player wimp. Hitchcock might have been served better by going with the other actor rumoured to have been considered for Granger's part - William Holden. The handsome soullessness he displayed in Sunset Boulevard would have been just the right quality for this role, something to make the audience doubt whether he actually wanted his ex-wife dead or not.
2. John Mills in Great Expectations
Simply too old to be a twentysomething Pip. It fairly ruined the film for me, despite all that lovely camerawork and Alec Guinness as Herbert Pocket. Replacement would have to be Brit, and young at the time. How about Marius Goring, the ernest conductor in The Red Shoes?
3. Tom Hanks in The Da Vinci Code
Hanks is one my all-time favourites, but he lacked energy and a certain Indiana Jones-ness in this movie. A terrific replacement, to my mind, would be the talented Hugh Laurie, who's proved more than capable of putting on an American accent when required.
4. Paul Dano in There Will Be Blood
PT Anderson is almost as good a caster as his friend, Quiten Tarantino, this is the only role I can recall where I feel he slipped up. Dano tries hard, but Daniel Day-Lewis's performance is monstrously powerful, and Eli ends up seeming weak. Edward Norton would have fit the bill a lot better in my book (though he's a bit old). And how about Jesse Eisenberg?
5. Richard Gere in Days of Heaven
It's a magical, painterly film, but Gere doesn't make half the impact he should, and Sam Shepard's low-key performance overtakes his easily. John Travolta, originally considered for the role, might have brought more charisma to the table, as might Jeff Bridges, or even (I'm going out on a limb) Kevin Costner.
6. Norah Jones in My Blueberry Nights
Wong Kar-Wai had had some success with casting pop stars in lead roles before (most notably Faye Wong in Chungking Express). It backfired, however, with the beautiful but visibly nervous Norah Jones in this, his only English-language film. Cat Power's chemistry with Jude Law in a small cameo indicates that Kar-Wai may have cast the wrong smoky-voiced singer in the lead role. Natalie Portman (there's also Rachel Weisz, in case you think this film could accomodate any more astoundingly beautiful women), stealing scenes like a professional thief, would have done even better.