Personally I dont care at all if the setting is new or not, just that it is interesting.
Dragon Age is a perfect example there, I have never hated a setting in a game quite as much as that, so generic, so bland, so.... Tolkien. I played origins through for the interesting characters but I couldnt care less if everyone else in whatever the hell it was called land died. And the newest one just shifted from generic England rip-off to generic France rip-off.
I have pretty specific tastes with the setting and for me they make or break the game beyond anything else. BG1 was a bit too generic Europe setting for me, BG2 was excellent with the more colourful and alien environment. Morrowind was my all time favorite while Oblivion was barely playable rubbish. Some of my favorites have been games like Mass Effect, Gothic and Arx Fatalis, original games that just had a unique and memorable setting.
I generally hate turnbased games but I am really looking forward to the new Torment, that has to be potentially the most interesting setting I have heard of.
Basically if the setting is interesting I will love this game beyond all measure, if it feels like middle ages england with rip-off Tolkien races I will be lucky to break 10 hours before I give up.