Up also went a bit bland and rote in its plotting after the house arrived in South America, regardless of the perfection of that first sequence. My point being that I'd be willing to bet that what sold the movie to the millions that went to see it was the by-the-numbers adventure part and not the sweet, beautiful, sad and wonderful part.
Incidentally, a similar thing happened with Wall-e which took a nosedive after the little guy left the planet.
I think you're overstating that part about Up - the opening sequence was definitely the best part but the adventure part wasn't completely by the numbers, plus it was littered with beautiful, emotional bits as well.
I agree with Wall-E, though. It all kindof falls apart the moment humans appear.