Well the main difference is that you're not a "chief" at all.
You're human. No shields, no power armor. Just health. So unlike the other games, there's nothing to keep your health from going down, and the enemies are not your equal. They are tougher, and there are more of them. Tactics will win the game, not brute force like Halo 3.
There's also a bit more plot and emotional baggage. You're searching the remnants of a ruined city, and find dead comrades on the way. Unlike the Master Chief, where every soldier is inferior, you play a soldier who is just as mortal as the bodies he finds. He is constantly faced with overwhelming odds and his own mortality.
Less emphasis on shooting, and more about staying alive.
