How about Dave Eggers’ A Heartbreaking Work of Staggering Genius? It’s a memoir, so that counts as non-fiction, right?
While easy reading, The Man Who Mistook His Wife For a Hat by Oliver Sacks is funny, poignant, oddly unsettling and profoundly thought provoking, all at the same time. The book is a series of case studies about people with highly unusual neurological conditions. It’s the kind of book you’ll want to get a friend to read so you’ll have someone to discuss it with.
I always suggest Driving Mr. Albert by Michael Paterniti. Journalist and crazy scientist drive across the country to deliver Albert Einstein’s brain to his niece. Strange, funny and poignant.