SPEAK (part of the Penguin group), 2008.
This is a general teen-age angst and coming of age story, except better...
Q has had a long-time crush on his childhood friend Margo; unfortunately, since the 4th grade she has largely ignored him, entering into the ranks of the popular kids, something that Q clearly is not. It is important to note that Margo is not a typical popular girl; she is a T type personality who does crazy things with no regard for the consequences, and doesn't really fit in with any group -- hence her allure. This social hierarchy is violently disrupted in the senior year of high school, when her boyfriend cheats on Margo and her 'friends' neglect to tell her about it.
The Margo solution for this is an epic revenge quest. Lacking her regular posse, she decides to enlist Q. She does this by appearing outside his bedroom window in the middle of the night and demanding he chauffeur her around town. Which he does. After a night of pranking the popular kids in inventive and highly vindictive ways (and breaking into SeaWorld, 'cus, why not?) Margo disappears.
This is not the first time she's run off, and she's just turned 18. Between these two facts, the police are not particularly interested in the case. Margo's parents are so sick of her high jinks that they are changing the locks and hoping she stays gone. And truth be told, even Q isn't worried; he's pretty sure she'll be back in a few days. But as her absence becomes longer, he starts to think about some of the things she said on that last night, and he starts to worry that she may have been thinking of suicide -- and the more he thinks about it, the more likely this seems to be.
There is one hope; Margo always leaves clues as to where she is running off to -- usually ones so cryptic that no one can figure them out, but it quickly becomes apparent that she has left a (fairly cryptic) set of clues targeted specifically at Q. And so the hunt begins.
Which is all very interesting (more so than I have been able to express here), but the main themes of the book are actually dealing with people. Particularly Margo, who is a particularly odd person, but also Q's various friends, who, while helpful, are frustratingly obsessed with the prom and graduation, and his enemies, who turn out to be more human than he expected (but still mostly jerks). Q has various well-written revelations about how we relate to other people throughout the book; this is usually not as hokey as it sounds.
John Green is a quite popular author, but unfortunately I have not read any of his other books (except for the excellent-but-short Zombicorns), so I cannot compare this book to his usual works. I have been told by a couple of his fans that this is one of his best, and it is indeed pretty great. It is a bit teenager-y, but I think it is still enjoyable by those who are older. I found the first hundred pages moderately engaging, but after that it quickly became better, to the point where by the last few chapters the book became unputdownable. It was certainly good enough to convince me to read more of his works.
Paper Towns also won the 2009 Edgar Award for best Young Adult novel. Oh, and this is one of those rare books that have a poem as a central plot point and running theme, namely Walt Whitman's Song of Myself.
Warning: Frizz_K_West's writeup below, while excellent, has excessive spoilers.