This!
They could've replaced Tobey and especially Dunst blindfolded. May, Ben, Connors and Capt. Stacy, while not very easy to replace, worked.
While Dafoe won't be easy to replace at all as Norman, I still think there should be better options out there when it comes to looks, and Norman should be more cold and calculating this time. More psychopath ala 90's Norman and less schizo Norman. However, his Green Goblin will be hard to replace I think!
Jameson, Doc Ock and Harry however will be extremely hard to replace!