Spells, maneuvers, and many other class features are now powers. Powers come in at-will, per-encounter, and daily flavors. Your class gives you two at-will powers (chosen from four or five) which last your whole career, and you get a new power from your class every other level. Thus, all class progressions are the same as eachother, but have more options than a 3E one. Multiclassing is done by grabbing feats that let you swap your powers out for ones from another class; the number of these you can do is limited.
Each class has a role - this is nothing new, but now they admit to it in the book. The roles are better than the classic 4, and very reminiscent of City of Heroes (not WoW, which you will hear far too often). Monsters, too, have roles; and they are expected to be used in parties. Characters have strict tiers of power: heroic, paragon, and epic. Paragon characters get a paragon path: something like a gestalt prestige class. Epic characters get an epic destiny (same idea). You can replace your paragon path with farther multiclassing if you already picked up all the multiclassing feats.
Full attacks are gone, 5' steps (now 1square slides) are move-equivalent actions.
Most races give you a series of minor bonuses and a power of some sort. These powers can get very useful.
(That's all I can think of)