I plan (hope) to spend more time this year gaming with my friends who don't really game, or don't game at all. It's something I really like doing, and I've had great luck with it. It helps to think of it as "something we'll do this one time", rather than looking at it like you would a more serious regular gaming group.
I was planning a few things, and I realized that, of the games I personally own and play and love, there are three clear and distinct categories:
Games I would totally play with my non-gamer friends: Fiasco*, Shab al-hiri Roach, In A Wicked Age*, Lady Blackbird, old-school D&D (pre-1980)
Games I *might* play with my non-gamer friends, depending: Spirit of the Century, Mountain Witch, Dogs in the Vineyard, Dust Devils
Games I would never play with my non-gamer friends: Mouse Guard, Burning Wheel, D&D (Red Box, AD&D, 2E, 3E, 4E), Savage Worlds
* denotes a game I actually have played with non-gamer friends
These are very clear in my mind, although I'm not sure exactly WHAT made me categorize them as such. It's not really setting. Mostly mechanics, ease of pitch, front-loaded entertainment value, etc.
It's like pornography. I can't quite define it, but I know it when I see it.