I've been ruminating on this for quite a while now, and below is what I've come up with. Note these are in no particular order except in which I thought of them -- which is probably meaningful enough, right there.
1. Philip K. Dick's The Man in the High Castle. For me this is a desert island book by any definition you care to name. It would even be on my list if that list were merely of objects of any kind. Fire starter, soap, water bottle, knife, Man in the High Castle. I do not exaggerate. Something to occupy the mind is as vital as being able to catch and kill and cook and eat, and this book has everything I look for in a good read: provocative ideas (like an alternate history in which the Axis won WWII and Germany and Japan divided up North America between them), delicate passages of philosophical speculation, sensitive characterizations and a weird plot that feels a little different every time I read it. Dick always claimed that the I Ching wrote this novel and he's just the dude that cast the yarrow stalks. Whether you believe in that stuff or not, the result is unlike anything you'll ever read.
2. John Brunner's The Sheep Look Up. Self-denying prophecy you should thank whatever you believe in didn't come true, combined with a fascinating series of intertwined plots. Because Desert Island reading shouldn't always be comfort reading. Click on the linked title for my original blog post on it. I've only read it once, but I know I'll be returning to it again and again. I'm a bit of a masochist that way.
3. Tim Powers' Last Call. Really, it's a toss-up for me between this one and The Anubis Gates, but I knew that one of them had to be on this list. This is another book that ticks every box for me, in which the archetypes of the Tarot meet the warty fat man in the famous Mandelbrot fractal and Bugsy Siegel was once the Fisher King of the American West. I could almost recite it by heart, but I have yet to tire of it, and I've read it probably even more times than I've read The Man in the High Castle (but only because I got my hands on this one first).
4. Theodore Sturgeon's Godbody. Far more than simply a parable-with-Jesus-figure, Theodore Sturgeon's last (and best) novel is just good medicine. It might be argued that this is literary, rather than speculative fiction; its miracles are of understanding and of the power of fellowship and love (brotherly more than romantic), its technical achievement -- each chapter is written by a different character, in the first person, and Sturgeon gives each narrator such a distinctive voice that fellow spec fic master Robert A. Heinlein famously observed that if you had someone pick a page at random and read it aloud to you, you could tell instantly which character was speaking within just a line or two -- one I wish were more widely known and appreciated by the mainstream. This is the book I turn to when despair or serious biting misanthropy threaten to overtake me. I'm always the better for enjoying it again.
5. Harlan Ellilson's Angry Candy. Many might argue that Unca Harlan has produced better short story collections, or at least more famous ones, but this one holds the most deeply felt and personal significance for me. Each story -- and its howlingly bitter and painful-to-read preface by the author -- is a reaction to the grim realities of death and loss. Sometimes it treats of the grieving process, or what happens when you get stuck in it, as does "The Function of Dream Sleep" (the single most important short story in my world). Others speculate on what might be done with one last hour of time that's been knocked loose in the universe -- who wouldn't want to grab it for him or herself to spend with a lost loved one? -- and "The Paladin of the Lost Hour"'s role in protecting it from abuse. Then there's "Eidolons", telling a bizarre story in a series of searingly wonderful aphorisms and passages like this one:
Did you have one of those days today, like a nail in the foot? Did the pterodactyl corpse dropped by the ghost of your mother from the spectral Hindenburg forever circling the Earth come smashing through the lid of your glass coffin? Did the New York strip steak you attacked at dinner suddenly show a mouth filled with needle-sharp teeth, and did it snap off the end of your fork, the last solid-gold fork from the set Anastasia pressed into your hands as they took her away to be shot? Is the slab under your apartment building moaning that it cannot stand the weight on its back a moment longer, and is the building stretching and creaking? Did a good friend betray you today, or did that good friend merely keep silent and fail to come to your aid? Are you holding the razor at your throat this very instant? Take heart, comfort is at hand. This is the hour that stretches. Djam karet. We are the cavalry. We're here. Put away the pills. We'll get you through this bloody night. Next time, it'll be your turn to help us.
7. Jorge Luis Borges' Labyrinths. My first and still my favorite Borges collection, at least that could by any stretch be included as speculative fiction (his poetry collection The Gold of the Tigers would bump it a bit on a more general books list). This is a bit of a sneaky choice on my part since it includes some of Borges' essays as well, but hey, it also has most of his greatest thought-experiment-cum-short-stories, in which his characters rewrite Don Quixote word for word from scratch and thereby produce a "richer" version of the original, dream up a whole 'nother human being fiber by fiber and actually creates that being, and a condemned man makes his last minute of life stretch into infinity. To name just a few. Borges inspired pretty much everyone else in the genre whom I respect; he still blows me away to this day.
8. Gene Wolfe's Book of the New Sun. All twelve volumes of it. Yes, this is totally cheating. What are you going to do about it. I'm not afraid of you? Well, I might be afraid of you if you're Matt Wallace, but actually I had a drink with him once and found him very pleasant company, so there. Anyway, Wolfe's tightly written yet sprawling, maddeningly obtuse is-this-the-past-or-the-future-or-the-present-or-all-of-it science fiction/fantasy hybrid about an ordinary guy (who might be a god but then again might just be some schmo) who somehow winds up tasked with traveling across time and space to find the McGuffin That Will Reignite the Sun (and who also may or not be 1. Along for the ride on a generational spaceship in the form of a hollowed-out comet and 2. Living amongst the weird inhabitants of the dual planetary system to which that ship travels, which system might just actually be Earth/Urth depending on which theory) will no doubt keep me scratching my head and dropping my jaw for the rest of my life. I develop a different theory about what's going on every single time. And I promise I'll get back to the Suns Suns Suns post series soon. Because there is SO MUCH MORE I want to say about these books. Oh, and the above cover to the very first book, Shadow of the Torturer, is one of my favorite book covers of all time.
9. Clark Thomas Carlton's Prophets of the Ghost Ants. Is this one of the greatest works of speculative fiction of all time? Probably not. But this is my list, and of all the books I've ever read, this one feels the most like it was written just for me, and I love it. It's got insects galore (a key to my happiness, six-legged arthopods), a well-done, an admittedly kind of standard fantasy plot but with peculiar Dune-like grace notes that are all about individual vs collective choices and question very strongly the role of religion and received belief in any life that could remotely be called human ,well-realized and imaginative world-building, and did I mention insects? Ants, roaches, wasps, more ants, termites, beetles... you get the idea. True, I might get sick of it if I'm stuck on that desert island for decades, but you know that by then I'll be writing Antasy fan fiction on palm leaves in my own blood by then anyway.
10. Alastair Reynold's Century Rain. Reynolds is my favorite living science fiction author, as I have said many times on his blog. When it comes to one of his books, it's not a question of love or merely like (let alone dislike), but only of how intensely do I love. This story of a future archaeologist who has built a career on investigating the aftermath of a nanotech disaster that made Earth uninhabitable, and the weird planet-sized diorama of mid 20th century Earth that is discovered at the end of a wormhole in space is loaded with gorgeous details, eerie speculation, cosmic awe, factional tension and just plain awesomeness. I would prefer to just get to take all of my Reynolds with me, but if I had to pick just one, it would be this. Just because it's so pretty and jazzy and lovely and cool.
Honorable mentions, just because: Frank Herbert's Dune, Bruce Sterling's Distraction, Ken MacLeod's The Star Fraction, Hugh Howey's Wool Omnibus and Ramez Naam's Nexus.