Personally, I think the decline of 2-D animated films had more to do with an overall decline of story quality. Think about the great animated films of the 80s and early 90s, some of which have been mentioned here. In particular, I think that The Land Before Time (the first one, NOT the awful AWFUL video sequels) is one of the finest animated films I've seen. That dark imagery, that beautiful James Horner score, the amazingly grim and sad story.
It seems to me that from Pocahontas onward, Disney stopped trying. They realized they could make money by just slapping something together with talking animals that can be easily turned into toys and put in McDonalds meals. I suppose it's worth mentioning that Pixar's first film, Toy Story, came out in the exact same year as Pocahontas. Quite the contrast.
I think that if a 2-D film with a really great story came along, it would do well. It's a shame that Don Bluth, who directed Land Before Time, Secret of Nimh, and others for Universal, has been inactive for about ten years now. Brad Bird made The Iron Giant in 1999, which I loved, but Pixar snatched him up fast for The Incredibles.
As for Miyazaki, he's been on the cusp of retirement for years now..the only other anime director who I really respect is Satoshi Kon (Perfect Blue, Millennium Actress, Tokyo Godfathers). So the playing field will be pretty empty, unfortunately. Personally, I'm glad that Pixar has been putting so much effort into its stories (though Cars was much more formulaic than the others have been).
I've rambled on for a while, haven't I? I guess the point I really meant to make was this: It's not the medium, it's the story.