Right off the bat, I'm going to say that Y is the saddest story I have ever taken in, with an emotional punch like a locomotive (or a bomb if you will). No work of fiction has ever destroyed me emotionally like this has. That being said, the story may be a tragedy, but gettin there was a lot of fun.
The story starts off with every male mammal on the face of the Earth being almost simultaneously wiped out by some kind of illness. With the exception of English major/escape artist Yorick Brown, and Ampersand, a capuchin monkey that he's volunteered to train to help people with disabilities. There's no apparent reason as to why they survived, they just did. At the time the plague hit, Yorick's girlfriend, whom he was about to propose to, was on a trip in Australia, while he was in Chicago. Naturally he sets out to find his true love. Along the way he picks up the companions 355, an agent of a secret government organization called the Culper Ring, and Dr. Allison Mann, one of the world's foremost authorities on human cloning.
Together they cross the country, and eventually the globe, trying to keep Yorick from becoming common knowledge, and thus the center of riots and wars, while they can figure out how he survived, synthesize it and/or clone him. They have mixed success with that first objective, as one of his earliest exploits brings him to the attention of a group that call themselves The Daughters of the Amazons, women who believe that the Gendercide (as it later becomes known) was god's way of purging the Earth of Man's wicked influence, they ritualistically burn/cut off their left breasts to emulate the Amazons of old, and are generally very scary extremists.
I don't want to go too much further into the story, because there's a lot of great things there, and I'd risk spoiling, and thus lessening the emotional impact of what happens.
I'm not sure why it is that this story hits so much harder than any other I've seen, I think movies just can't compare on account of their being too short for you to really bond with any of the characters, I read a lot less prose tragedies, so I don't know if it's necessary a medium there, or if I'm just underexposed. The bottom line is that I love the characters in this book, and I'm very sad that they're story is over.