Are we guilty of confusing favourite with best?
I considered this, in relation to my own list of SF novels, but I think with the OP's phrasing of the thread title I am fine with
The Mote in God's Eye being my own, subjectively chosen, greatest SF novel.
If I was asked to give a choice of the greatest work of literary SF, well I'd happily cross off
Mote, and pick
1984, or some other brilliant book (I greatly admire the very bleak
1984 as fiction). But it's mostly subjective (though I can say, for example, Keith Laumer would never make my own list, though some of his books are fine), and if I could only ever read one last SF novel before my time here was done, I am pretty confident it would be
Mote. (It might help that I read it within a year or so of its being published. It was one of my first SF novels, and has possibly an inherent, unfair advantage in choosing a greatest, over any other novel on my list.) So it might be my favorite, yes, but it was also probably my greatest SF reading experience, for the story and aliens (if not the quality of the writing).
Well, I am blathering. Great fun seeing everyone's choices, CC