For starters, 2 has much more varied gameplay. At launch, the first L4D had four campaigns that were more or less identical--they all played out the same way but they took place on different maps. The five campaigns in the sequel all have their own unique flavors. Dead Center goes for the zombie-slasher-flick vibe full-bore. It has the most plot-centric progression, it has none-too-subtle nods to other zombie movies (the last half of the campaign takes place in a mall).
Dark Carnival feels like a pretty straight-forward L4D experience, but Swamp Fever has a much more open-world vibe. Hard Rain is probably the most survival-horror of them, and the go-there-and-come-back nature of the level makes it stand out. The Parish in many ways feel like the epitome of what a L4D2 campaign is. The panic events are nearly all in the new gauntlet style, and it has the only gauntlet-style finale, in which you run across a bridge against a head-on cavalcade of infected.
The other substantial difference between this game and its predecessor is that the maps feel much more open--the maps in the original game had plenty of areas to explore, but the areas were tighter-quartered. The openness of the sequel means that the special infected can't sneak up on you as easily and are easier to defend against. They counteract this by throwing even more of them at you. Just this evening I came to a safe room only to be set upon by a Jockey and two Hunters.
Still enjoying it very much, though.