You know what'd make this game different and fresh? NOT HAVING A TWIST ENDING. The first one was admittedly fantastic, so instead of trying to live up to it, how about we just don't put in a twist? The twist would be NOT HAVING A TWIST.
But it probably will and it'll be something lame and semi-canon breaking like Tenenbaum being the Big Sister, or something. The problem is that would be a fine twist, if people weren't expecting a twist.
Bioshock is the movie The Sixth Sense, and Bioshock 2 will be every thriller movie AFTER The Sixth Sense. Arbitary twist-ville.
But apart from that, I think bringing a new perspective to the game rather than just having Bioshock 2: Jack's Back was a good move. I also think the vulnerability will be there, seeing as the game mostly revolves around you being stalked by the Big Sister, not knowing where she is at any time.
I think it won't be a failure, it just won't be as earth shattering as Bioshock.