If at first Hugo Weaving said that he has no interest in reprising the role of the Red Skull in any Captain America movie following The First Avenger, the actor said that he has no clue whether the character will come back for Captain America: Civil War –
I have absolutely no idea. I haven’t talked to anyone about it, so yeah, we’ll just have to wait and see. No idea at all.”
The most recent casting for The Winter Soldier sequel is that of Daniel Bruhl, who is most likely to be Baron Zemo. If that happens, there are little to no chances of seeing the Red Skull again.
However, this wouldn't be the first time when an actor changes his mind. And since Hugo Weaving dodges the question, or at least doesn't stick to what he first said, we might see the iconic character once again (and, who knows, maybe he will order the assassination of Steve Rogers, just like in the comics).
Source: Comic Book Movie