If you get to be Clancy Brown, can I be Frank Welker?
Also, perhaps stretching “superhero,” Buffy.
Before getting cast as James Bond, young Timothy Dalton picked up a comic-book credit as a sword-wielding Prince Barin in the Flash Gordon movie; he later played an eyepatch-wearing Basil St. John in the Brenda Starr movie; and while his role as Neville Sinclair in The Rocketeer was apparently created for the film and so doesn’t count, I’m not gonna not mention it because that movie was awesome.
Thomas Haden Church - Sandman (Spider-Man 3) and the Strobe (The Specials).
And I don’t know what the OP is talking about. Deadpool has never been in a live action movie. He should star in Highlander 2.
Richard Roxburgh was Sherlock Holmes in a Hound of the Baskervilles TV movie in '02; in '03, he was ‘M’ in The League Of Extraordinary Gentlemen; and in '04 he was Dracula opposite Hugh Jackman’s Van Helsing.
Another example: character actor Lyle Talbot, probably best remembered today as the police detective rubbing his chin with a loaded pistol in Plan Nine From Outer Space essayed early versions of famous DC characters in Republic series.
Luthor (before ‘Superboy’ named him Lex)
Commissioner Gordon (the Bat Signal also debuted in a small handheld version )
Technically, Chris Evans also played Loki in Thor 2. Or, at least, played Loki impersonating Captain America.
Oh, here’s another one (if you include characters with a comic connection instead of originating in comics): Cesar Romero
The Joker
The Cisco Kid
Dracula (in the jokey blood bank Night Gallery episode)
I already mentioned him in post #9.
A few years after he was Count Dracula, Bela Lugosi got a rare good-guy role as Chandu. Now, you could argue for a definition of ‘superhero’ that excludes Frank Chandler – but he’s, well, a super-powered hero, using his extraordinary abilities to fight crime and save lives under an assumed name, so, y’know, yeah.
(Besides, he really sells that whole Mandrake-the-Magician schtick with his famous loooook into my eeeeeeyes routine, which deserves the benefit of the doubt.)
Ryan Reynolds played Wade Wilson in X-Men Origins: Wolverine. I don’t think he’s explicitly called Deadpool at any time, but it’s the same guy, as verified here.
Neil Patrick Harris voiced Music Meister in Batman: The Brave and the Bold and of course was Dr. Horrible (who did not originate in a comic but was in a comic about his origins, if that makes sense).
If Sarah Connor counts, Christian Bale has played Batman and John Connor.
Also Balrog/M. Bison in Street Fighter: The Legend of Chun-Li and the voice of Kilowog in The Green Lantern.
Bumping this because I only just now remembered that Jon Favreau was Foggy Nelson in Daredevil before he started playing Happy Hogan in the Iron Man movies.
(You remember the Iron Man movies, right? The ones starring Sherlock Holmes?)
Mar Elizabeth Winstead played Ramona Flowers in Scott Pilgrim vs The World, and Gwen Grayson in Sky High. She was also Mary Todd Lincoln in Abraham Lincoln:Vampire Hunter but I’m not sure that counts as a superhero movie…
The last thing michael Clark Duncan did before he passed away was voice Groot in an animated Guardians of the Galaxy cartoon.