Middlesex

Yes, this is technically the story of a hermaphrodite, but sex is not a big part of this story. As another reviewer has said, it really is an epic story of America told through the history of several generations of a family. Callie is a real, human character -- not even born through much of the book, a child for most of the rest -- whose unusual sexual status is not at all the focus of the book.

Especially if you have connections to the upper Midwest, you'll love the details of Michigan history, which are never dry.

Virtuoso writing, too, and if you are a literature buff you'll appreciate the allusions. If you've read Tristram Shandy, Middlesex is required for you, but if not, it won't matter a whit.