Setting is probably the most important factor in whether or not I like a game. Let me put it this way: I don't play Teenage Mutant Ninja Turtles & Other Strangeness for the system. The Palladium system is fine, it just doesn't light me on fire. The setting... Ooooo the setting! Distilled lightning in a jar! I think most folks are like me in that respect, that setting sells games.
So why do I fill this blog up with system toys and tools? Because a given setting either works for you or it doesn't. There are only two basic parameters in Setting - Breadth and Depth - and beyond that, there is nothing much you can use as a tool to help you create. It's either there or it isn't. I come up with settings all the time - very few of them ever see print. I know I have a winner when a setting refuses to let me go, when it takes me by the scruff of the neck and hauls me in. If it doesn't do that... meh! It's all subjective. Taste-driven. No *tools*.
On the other hand, I believe strongly that systems should be tailored to their settings. Sub-systems should reflect the genre and special flavor of the setting. Slapping a good generic system into a good setting does *not* make a good game. When the designer is done, ideally the intended setting could be taken out yet still be strongly implied by the mechanics.