Fans have mostly believed since his character's death at the end of Captain America: The First Avenger that Weaving would return at some point, given the fact that nobody stays dead forever in superhero stories and Skull plays a pivotal role in The Winter Soldier, Ed Brubaker's Captain America arc upon which the second film is based.
"I think the tendency, with those films, would be to probably not bring a villain back," Weaving said of big superhero tentpoles. "They might for The Avengers, but I didn’t think I’d be in Captain America 2 or 3. I don’t think Red Skull will be there. And it’s not something I would want to do again. I’m glad I did it. I did sign up for a number of pictures and I suppose, contractually, I would be obliged to, if they forced me to, but they wouldn’t want to force someone to do it, if they didn’t want to.
It could be a conversation we hear again down the road, of course--while he's likely right that Marvel wouldn't have any particualr desire to bring him back if he didn't want to do the film, the fact that he's signed on the dotted line could create a problem either for Weaving or for Marvel when it comes time to re-cast should the character turn out not to be quite as dead as advertised. Of course, the Iron Man and Incredible Hulk films have shown us that the studio isn't particularly shy about re-casting roles when the circumstances arise.