By greatest, I suppose I mean the highest achievement in both imaginative scope and literary execution. If you prefer, you could replace the word greatest with favorite and you would still be accurate.
Here are my choices:
Childhood’s End – Arthur Clarke
Dune – Frank Herbert
Stranger in a Strange Land - Robert Heinlein
A Canticle for Leibowitz – Walter M. Miller Jr.
20,000 Leagues under the Sea – Jules Verne
City - Clifford D. Simak
Dhalgren – Samuel R. Delaney
The Left Hand of Darkness – Ursula LeGuin
The End of Eternity – Isaac Azimov
To Your Scattered Bodies Go – Phillip Jose Farmer
Note: I have included only books I have read (usually many times). I have arbitrarily excluded such excellent series as the Lensman series by E.E. Doc Smith, the Foundation series by Isaac Asimov, and the Space Trilogy by C. S. Lewis, though I have included the first book of the Riverworld series because I feel it can stand alone. I have also excluded excellent novels that I consider primarily social critiques such as Slaughterhouse-5, 1984, Fahrenheit 451, A Clockwork Orange, and books I considered primarily fantasy. I have also generally excluded linked stories – though you could argue both City and Childhood’s End would qualify (I don’t).
So that's my list. What's yours? If you don't have one, this may be a good place to start exploring.