This is in comic based films and also outside of them. Just a few that come to mind.
Crispin Glover in 'Willard'
Vincent Price in 'Jackals'
R. Lee Ermey in 'Texas Chainsaw remakes'
Christopher Walken in 'Domino'
Robert Downey Jr. in 'In Dreams'
Johnny Depp in 'From Hell'
Christopher Lee in 'Police Academy 7'
Malcolm McDowell in 'Halloween remake'
John Glover in 'Batman & Robin'
Evans and Chiklis in 'FF 1 and 2'
Billy Zane in 'The Phantom'
Mia Kirshner in 'Crow: City of Angels'
Jon Cryer in 'Superman IV'
Dolph Lundgren in 'Punisher 89'
Frank Langella in 'Masters of the Universe'
David Warner in 'TMNT 2'
Ian McKellen in 'The Shadow'
Timothy Dalton in 'The Rocketeer'
Ryan Reynolds in 'Blade Trinity'
Sean Connery in 'League of Extraordinary Gentlemen'
Bruce Campbell - Spider-Man 3
Ryan Reynolds - Blade: Trinity (Though, this too was out of character! But he just resembled Deadpool so much so I kinda liked it because of that.)
James Marsden - X-Men: The Last Stand (Well, gotta say Cyclops wouldn't mourn like that...)
Routh as Superman/Kal El/Clark Kent.
He did such a fine job playing those that character, despite a movie with so many plot wholes and bad story telling.
I would love to see him play Superman again, just maybe in the JLA film instead of a Superman sequal.