It's a ground-up reboot of the engine. It's still a FPS, and the factions within the war are the same, but the game itself is spankin' new.
The most conspicuous new thing is that you have to choose between "character classes" now. There are 4 that I know of... Guards (who can become invincible on demand), Scouts (who can sprint), Airborne (who can fly with jetpacks) and Stealth (who can become invisible on demand). If you play as Covenent, there are other classes you can choose, but I've forgotten the details. I only played as Convenant a few times.
The physics are all upgraded, there are more cool weapons, and the existing weapons have been re-geared a little to add realism. The visuals are more realistic and gritty. The interface and HUD is different as well. And it replaces the flashlight with way superior Night-Vision (bonus: the Night Vision adds IFF enhancements to visuals).
I havent played the campaign (obviously), but I was part of the Multiplayer Beta test back in May, and I have thought of little else since then. There are a couple new enemies in the campaign (Jackal Skirmisher), and there are Firefight missions like in Halo:ODST (which probably means nothing to you unless you played ODST).
But yeah, if you stopped playing after Halo: Combat Evolved, then this will be an entirely new experience inside and out.