hyperflare mentioned "Hitchhiker's Guide", which is a fantastic choice. I think it's the only one in these comments that I think is an unambiguous shoo-in, although OftenBen's suggestion of "Stranger in a Strange Land" is also a good one. I love Asimov and Arthur C. Clarke to death — I grew up on them — but nowadays I don't really know that I'd classify them as good sci-fi. Important, maybe, for historical reasons, but if you want to show off the best of what sci-fi can do then I think there are better choices. Can I get any love for these? - Fahrenheit 451 by Ray Bradbury - Brave New World by Aldous Huxley - Cat's Cradle by Kurt Vonnegut (I'd also accept Sirens of Titan here, but personally I like Cradle better) - The Cyberiad by Stanisław Lem - We by Yevgeny Zamyatin - The Anything Box by Zenna Henderson - The Stars My Destination by Alfred Bester (though The Demolished Man is a good choice too) - Flowers for Algernon by Daniel Keyes Most of these probably speak for themselves, but I do want to say that Lem is probably a lot better than you expect him to be. He's best known for Solaris, which is a dense, difficult book. The Cyberiad, by contrast, is a complete delight, and one of the funniest books I've ever read. I also want to put in a plug for Zenna Henderson, whose short story collection The Anything Box I included in my list. She's the best sci-fi author no-one's ever heard of. In a male-dominated genre in a male-dominated time (the 1950s), when most people were writing about spaceships and lasers and robots, Henderson wrote these amazing, beautiful, touching, domestic sci-fi stories, often featuring children and families. Her work is amazing, and I really hope that one day the world will rediscover what a gem she was.
Eeeeee, someone else who's read the short story! I'm on your side. The short story was my first exposure to Algernon so I'll always love it more, but it's a great read either way. If you're anything like me you have a reading list a mile long, but if you get the chance to read some of Henderson's stuff I'd love to hear what you think.