What differentiates The Witcher 2 from other WRPGs? I'm not very fond of them but this looks quite good and I keep on hearing great things about the story. I've played, from this generation: Dragon Age 1 + Expansion, Fallout 3, Mass Effect 1, Fable 2 and I've only kind of enjoyed Dragon Age.
Well for one thing, unlike all the WRPG's you've played this gen it follows a singular character, Geralt. This alone means there's a greater emphasis on characterization and your relationships with other characters seem genuine, as the writers have a lot of lore and the previous game to construct them from.
The games main focus is fairly political, it's more akin to 'A Game of Thrones' than any other game you've mentioned; there's no real ultimate evil ala Bioware games, every character simply has their own motivations and agenda's, and depending on your choices these motivations creates an interesting story. In short the story doesn't feel like it revolves entirely around Geralt. You play an important part sure, but events are a by product of other characters goals rather than any of the aforementioned games, whom all focus on making you the 'Chosen one'.
As a result the story is mature, engaging and defiantly a step in the right direction for video-games in general. Though obviously your taste's may vary.
Combat is akin to Batman : Arkham Asylum [apparently the system was inspired by it] so it's very rhythm focused, relying on you reading and adapting to the system and enemies combat style. The system is fairly simplistic, but there's enough depth in there for combat to remain engaging. If you wanted to compare it to anything on your list a more complex Fable would be the answer.
The real difference comes in the choices. As others have mentioned everything is grey in this game, and your choices have real impact - more so than the series you've mentioned. Your choices effect where you go, who you meet, character motivations and so on. The game really requires multiple playthroughs there's so much content you'll miss due to choices.