George Orwell, if he'd lived longer, would have gotten the Nobel Prize, chiefly for Nineteen Eighty-Four, one of the greatest masterpieces of English literature. And s-f, definitely. The first paperback edition in the U.S. was even flagrantly marketed as such with a wonderfully schlocky cover.
Regarding Heinlein, he is obviously the most influential figure in the history of genre s-f and indeed one of the most influential American literary figures of the middle 20th century, period--you see his influence in the space program, today's Mars program, libertarianism, the Second Amendment movement, the hippie movement, the sexual revolution, the transgender movement, even the civil rights movement in that he was an early and consistent anti-racist. He also spoke out in his books against the religious extremism that morphed into today's Christian Right. If influence was a criteria for the Nobel Prize he would have been at the top of the list. Alas, I have to admit that with the exception of his children's books (which are great in a special way and never got the recognition they deserved from the appropriate prize committees) and Friday (a novel which almost attains the level of an important novel but is marred by some sloppy pulpish plotting) his work never gets there in a literary sense and some of his ideas are, frankly, half baked. Too bad, because I love the guy's work overall, and after reading Citizen of the Galaxy as a kid I could never again tolerate singing "In Dixie Land..."
A similar problem arises with Conan Doyle. What do you do with a writer who creates the most memorable and best-loved characters in world literature--Holmes and Watson? And concocts in just a few paragraphs secondary characters such as Irene Adler, Prof. Moriarty, and Mycroft Holmes who also will live, like, forever? And contains some of the most quoted aphorisms in literature? And yet he puts all these elements in stories in which a literary quality is somewhat lacking (except in the short novel The Hound of the Baskervilles which I believe is on lists as being among the 50 or 100 greatest works of the 20th century). So what do you do with Doyle? You declare his work a tour de force and move on.
Finally, we are forgetting a Nobel Prize winner who did write one science-fiction short story: Winston Churchill, "If Lee Had Not Won the Battle of Gettysburg" (in the 1931 anthology If It Had Happened Otherwise), which may have influenced the 1953 s-f classic Bring the Jubilee by Ward Moore.