The developers responsible for Halo 4, 343 Industries, have the game pegged as the first instalment of the next trilogy, which will be marked with more character development and focus on the history of the Forerunners, creators of the Halos. Content and tone will also be "darker" according to most sources, which sounds about right since there are complications related to Cortana's lifespan and tendency toward insanity. It's explained much better in the "expanded universe" of books and short stories about how the idea of AI insanity (also known as "rampancy") plays out and why it happens.
Just based on that information and the fact a "4" appears after the title (and the available videos back this up), gamers can expect new enemies, new allies, character model tweaks and overhauls, new weapons, and likely new abilities. (I'm already imagining Master Chief outfitting his specialized armour with Forerunner tech in a montage that would make the A-Team proud.)
There's already a build-up for the title and it doesn't launch until November 6, 2012. Microsoft is putting a massive amount of money and resources into marketing the game already and we're still months from launch. Expectations are high and so far there's no reason to doubt that those expectations won't be satisfied.
- Aaron Simmer