The news currently hints that Kirsten 'Mary Jane' Dunst is either still in talks or that the studio is trying to decide how to announce her departure. I love my Kiki (despite that love winning me no fans) but I hope she's out. That'll give her more time to pursue more creative performance challenges. And as an added bonus if she departs: Mary Jane's absence would force the filmmaking team to come up with a new emotional dynamic rather than repeating themselves twice more. Comic book relationships do tend to cycle endlessly (Superman & Lois / Peter & Mary Jane / Scott Summers & various incarnations of Jean Grey) but in movies... well, that constant retelling dynamic doesn't work as well.
Sam Raimi is a resourceful, creative director. He should be able to find a way to keep Peter Parker's moony-eyed feelings in play even without his on again/off again girl in the mix. What's more, Raimi should. Spider-Man's unashamed earnestness (some might say corny sincerity) provide a nice counter-balance in the superhero movie culture. It's decidedly different than the stuff that's in vogue, i.e. the fanboy comfort
Good luck to all.