Dune
On the desert planet Arrakis, young Paul Atreides is thrust into a deadly struggle over the universe's most valuable substance: the spice melange. Herbert weaves ecology, religion, politics, and prophecy into the most fully realized world science fiction has ever produced.
Dune tops this list because no other novel matches its scope or influence — it is to science fiction what The Lord of the Rings is to fantasy, and its themes of ecology and charismatic power only grow more relevant.