Have you played Defense Grid? No? Go play it--play the whole damn thing--and then come back. Alright, now that you've beaten Defense Grid and you know how good it is, so we don't need to waste time telling you how it's one of the best tower defense games of all time. And from what we've seen from the sequel at PAX 2013, there's a good chance it'll be even better.
In the original game you were on the defensive, fighting against an invading alien force, but this time you're protecting other planets from little aliens set on stealing shiny orbs. To defeat them you'll need to, obviously, place down towers. Where DG2 spices things up is with the pathing and dynamic levels, both of which have the potential to change the genre. Pathing works as it does in most tower defense games, but the addition of a boost tower is a masterstroke--instead of placing down useless walls or low-level towers to force the enemies on a specific path, you can place cheap "boost" towers. These towers are inexpensive platforms that can have towers placed on top of them, which expands their line-of-sight to let you have multiple layers of towers.
The levels can change, too, making things even more complicated. At one point an entire new area opened up when a platform flew into place, allowing the player to force the enemies into a section of the map that simply wasn't available at first. There are plenty of other interesting features (items that can upgrade tower types, competitive multiplayer, co-op, heatmaps showing off your damage range, user-generated content, multiple characters) but you're going to have to wait until the beta comes out in November to see how they all work.
Check out the following slides for additional images and more information.