When I'm reading a role-playing book, nothing makes my eyes glaze over quicker than seeing a big pile of setting material. "These vampires don't like these other vampires, and these vampires are white-skinned, and these vampires like to cook..."
Setting material in the form of lists (here's all the characters you can be; here's a random list of monsters you might meet) are okay, because you aren't expected to know them, they're just reference, but still - if it's not a setting I'm interested in, I'm still going to be alienated. There might be a lot of good fantasy games out there that aren't D&D, but I'm done with fantasy, so it's a hard sell.
I wish I could find the quote I keep quoting: we love our children more than anyone else's, and that's particularly true when the children are ideas. Involve me in the setting creation, or let me and my friends create the setting completely!
Every game of In a Wicked Age I play, we sit down and create a little sketch of our bronze age fantasy environment. It's probably poorly drawn and rudimentary, but I love those worlds more than almost any other fantasy kingdom. (Middle Earth still wins.) Because those worlds are our children.
Of course, if you're a big company trying to make money, what are you going to do? You want to own some IP. You want a world you can set not only your games in, but you probably want to branch out into comics and novels and hopefully tv shows and movies.
Not to mention, you ask someone what draws them to a particular game, they're probably going to say: The Setting. "I like Vampire because it has vampires."
But for me, it's almost a no-brainer. I want to let people play in whatever setting they want. I don't want to own some IP; I want as many people playing it as possible. If someone's turned off by vampires and someone else is turned off by space opera and someone else is turned off by cop shows ... I still want them to be willing to try my game.
But how do I sell that? It's easy to say, "Hey, this game has vampires." It's hard to say, "This game has whatever you want." Because, honestly, if you really want a vampire game, a game that's first and foremost meant to be about vampires is probably going to do it better. So how?