IGN:
Captain America: The First Avenger's Hugo Weaving recently spoke quite candidly about the prospect of returning as Red Skull in future Captain America or Marvel films.
In a chat with Collider, Weaving said of the possibility of reprising his villain role in the future, "I think the tendency, with those films, would be to probably not bring a villain back. 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."
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Good news is that he can be re-cast and a simple explanation could be that when he was "sucked into" the Tesseract, it changed him. Problem solved.
Just bring back the Red Skull soon please.