Anything by Gene Wolfe is awesome and makes everyone else's fiction look like chump change in comparison. Even his weak stuff (An Evil Guest) is pretty good. He has been called by more than one critic the best living American author in any genre and is acknowledged by many great speculative fiction authors as the best living sci-fi writer alive.
My specific recommendation is his Solar Cycle, a series of books that are all awesome and filled with unreliable first person narrators and a crazy blend of sci-fi and fantasy that is very much unlike anything else. The Book of the New Sun (a tetralogy of four books, though it can be bought in one omnibus edition) about a disgraced torturer named Severian who is outcast from his order after giving one of his charges a painless death and his journey across a decaying planet with a dying sun. It also has a sequel called The Urth of the New Sun.
Loosely connected to the Book of the New Sun is the Book of the Long Sun (another tetralogy), about an augur named Silk who receives enlightenment from a god and attempts to save his church from being sold to a criminal named Blood. That is followed by the Book of the Short Sun (a trilogy this time), which is a direct sequel to the Book of the Long Sun and also serves as a very very tangential sequel to the Book of the New Sun, about a man named Horn, one of the former students of Silk, who goes on a journey to find Silk and bring him back.
Less science fictiony, but what I feel are Gene Wolfe's best work, are the Wizard Knight books. It's two books (the Wizard and the Knight) about a boy named Abel who is transported to a fantasy world, given the body of an adult, and his quest to earn the love of a nature spirit. In a similar vein is Pirate Freedom, about a boy living in a near-future Cuba who is transported back in time to the Golden Age of Piracy and ends up becoming a pirate himself.
And then there's the Soldier series, consisting of Solder of the Mist, Soldier of Arete, and Soldier of Sidon, about a Greek mercenary called Latro fighting in Rome who suffers a head wound in battle, suffers amnesia, and can no longer form long term memories. However, he becomes able to see the various gods of the ancient world. The novels are presented as scrolls that Latro records almost daily so that he has some record of his life as he tries to recover his memory and return home.
Then there's a dozen other great pieces from Wolfe, such as the Fifth Head of Cerberus (essentially three novellas about a planet being colonized in the far future), There Are Doors (about a man who travels between two dimensions to track down a woman he's in love with), and a bunch of collections of short stories.