SciFive. Via Peter Sean Bradley, here's one SciFi top five list and here's mine:

1. Frankenstein by Mary Shelley
2. Brave New World by Aldous Huxley
3. Ray Bradbury: Fahrenheit 451; Martian Chronicles, Illustrated Man.
4. The Stand by Stephen King
5. ...

Since I cheated with choice number 3, I'm not picking a 5th. (If I were, it would probably be Nineteen Eighty-Four.*)

Discussion

Prologue

To answer this question, one first must address what is Science Fiction? Here is a page which collects the definitions from a number of SciFi writers. I pick one from Robert A. Heinlein:

Science Fiction is speculative fiction in which the author takes as his first postulate the real world as we know it, including all established facts and natural laws. The result can be extremely fantastic in content, but it is not fantasy; it is legitimate--and often very tightly reasoned--speculation about the possibilities of the real world. This category excludes rocket ships that make U-turns, serpent men of Neptune that lust after human maidens, and stories by authors who flunked their Boy Scout merit badge tests in descriptive astronomy.
from: Ray Guns And Spaceships, in Expanded Universe, Ace, 1981

Accordingly, to me, the best science fiction is an extended meditation on the nature of man that begins with a premise: "What if...?" In some ways, it's like the economist who begins with "assume full employment." Assume that a plague has decimated the human race..., assume that a man can harness electricity and re-animate a dead human body... and so on.

My List

• Frankenstein or The Modern Prometheus by Mary Shelley. Some call this the first Science Fiction novel (although there is a good argument that the first SciFi story was Shakespeare's The Tempest [via Eric Rabkin lecture]). Others say it's a Gothic, still others say it's pure horror. Nonsense, it's science fiction. First of all, the novel is different from the classic movie. Dr. Frankenstein's creation is (or becomes) quite eloquent, yet without a conscience. It explores the relationship of man and his attempts to become like God and what it means for all of us. This novel, especially when set in the context of the literature of the time, is incredibly revolutionary. Notes
  

• The title of the novel Brave New World, by Aldous Huxley is taken from Miranda's dialogue in Shakespeare's The Tempest, mentioned above:

O, wonder!
How many goodly creatures are there here!
How beauteous mankind is! O brave new world
That has such people in't! (V.i.181-4)

It appears that in the future, we have achieved utopia -- we're all healthy and well-ordered Poverty and war are no more. We're all equal and happy (Soma). Okay, so we had to get rid of a few small things: God, family, literature, art, and philosophy, to name a few... Plus, we don't have to worry about pregnancy -- just take that magic pill (who needs Humanae Vitae?). Who needs love?**

• Bradbury. I have always loved Ray Bradbury -- he was my stepstone (thanks Mom!) into the world of Science Fiction (if you don't count the Danny Dunn books). And I can't pick just one! F451 is a dystopia consistent with the first two mentioned above. Yet, Bradbury is so poetic and lyrical in his descriptions -- I'd probably pick this just based on the title alone ("the temperature at which book-paper catches fire and burns ..."). Both the Martian Chronicles and the Illustrated Man are loose collections of short stories with common themes. In part, I like Bradbury because he writes anti-science fiction. In part, because he is a wonderful writer. In part, because he forecast the future so well. The iPod, the Wall-to-Wall, hidef TV, microwave ovens, the smart house, and others I am forgetting now, all appeared in these stories, back in the 1940s.
  

• The Stand. This comes in two version - the original release and the director's, err, author's uncut version. Essentially biological warfare preparation goes bad and a superbug, Captain Trips, is released killing 99.4% of the world's population. The book looks at three distinct events -- the release and decimation of society; the eventual gathering; and a showdown between the forces of light and of dark.
  

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*So why Brave New World and not 1984? In the foreword of Amusing Ourselves to Death (1986), Neil Postman compared the two worlds:

What Orwell feared were those who would ban books. What Huxley feared was that there would be no reason to ban a book, for there would be no one who wanted to read one. Orwell feared those who would deprive us of information. Huxley feared those who would give us so much that we would be reduced to passivity and egoism. Orwell feared that the truth would be concealed from us. Huxley feared the truth would be drowned in a sea of irrelevance. Orwell feared we would become a captive culture. Huxley feared we would become a trivial culture, preoccupied with some equivalent of the feelies, the orgy porgy, and the centrifugal bumblepuppy. As Huxley remarked in Brave New World Revisited, the civil libertarians and rationalists who are ever on the alert to oppose tyranny "failed to take into account man's almost infinite appetite for distractions." In 1984, Huxley added, people are controlled by inflicting pain. In Brave New World, they are controlled by inflicting pleasure. In short, Orwell feared that what we hate will ruin us. Huxley feared that what we love will ruin us.

While I think we need to guard against the abuses Orwell feared, I think Huxley's view is more likely.

** "Whoever wants to eliminate love is preparing to eliminate man as such."
Who wrote that? Huxley? No, Benny16

Deus Est Caritas (2006) via PSB