I think the thing that I'm the most interested in is the new Perks system, especially considering that during the course of a playthrough we'll only be able to select a maximum of 50 perks from the list of around 280 (according to Todd). This is awesome because it means that every character really is going to be different, not like Oblivion where once you reach end-game basically every character from every race winds up being pretty much the same (100 in all skills and attributes). It also leaves me with some questions, like will there be race specific perks? Or faction specific perks? Who knows but it's an idea that has a lot of potential
Let's hear from you guys and show Bethesda what we're looking forwards to in their new game!