I generally try to find a 'as close as I can get' western equivalent and/or comparison
EX:
Casshern Sins: "A violent version of 'Bicentennial Man'"
Last Exile: "Civil war in the Sky"
Serial Experiments Lain: "It's like 'The Matrix' before 'The Matrix'"
It's painful for me as a fan to try to sum up some of my favorite series this way, but honestly, I find it's easier for non-fans to grasp than "It's about a robot who's having an existential crisis amid the plague known as The Ruin, which he inadvertently caused by killing the Sun named Moon Luna, who was the only source of death in their world of immortality for both machine and humans."
I don't know what it is, but every time a family member or acquaintance asks me about a series, and I give the choice B as my first response, they always have a look on their face I can't quite discern, so I then give them a point of reference in Western popculture/ knowledge, and then they get it. I think having a point of reference to branch out from makes it easier to talk about it with someone who isn't an anime fan.
My favorite, too is having to explain to someone why the idea of a 22 year old dating a 12 year old isn't making me call PAC or some crap, and that it is indeed not that strange to find such age discrepancies in pairings in Anime and Manga, and even though it is odd, doesn't raise my concern. Or the idea of shipping and/or yaoi, and that there is INDEED a difference, so no I'm not A) reading pr0n in the middle of our Christmas get together, and B) although sex is about to happen in this story, it's not used as an important plot divice.