I’ve always thought that Heller’s God Knows is shamefully underrated.
The Summer Book by Tove Jansson.
Great novel, it’s like trying to pick your favorite child. Depends on your mood 
Not a single vote for Edith Wharton? (Unless I missed it upthread.) The Age of Innocence is one of my favorite novels of any century.
Deeply honorable mentions go to Confederacy of Dunces, Catch-22, The Old Man and the Sea, Foundation, Things Fall Apart, Slaughterhouse-5, etc. But I still think The Great Gatsby takes the cake.
another vote for Harper Lee,
While we’re at it In Cold Blood was pretty darned riveting
My favorites:
Greatest childhood: Call of the Wild by Jack London
Greatest teen: Lord of the Rings J.R.R. Tolkien
Greatest Adult: One Flew Over the Cuckoo’s Nest by Ken Kasey
Greatest Series: Foundation by Isaac Asimov
Very hard to nail down just one though
If we break it down into Categories, it would be easier to decide. At the risk of being hammered for starting with Science Fiction
Dune
My pick also–it’s not merely an “important” book, but it remains a cracking-good read.
I was just discussing 1984 this morning, I mentioned that the science fiction part of it seems unappreciated. This conversation was sparked by the news story about new smart TVs spying on viewers.
Orwell was a genius on so many levels.
This is the first I’ve heard of such a thing. Can you post a link?
I was stopping in to stump for The Master and Margarita and Titus Groan (the first novel in Peake’s Gormenghast series), but I see they’ve both been mentioned. TWICE, no less. So I’ll throw in
Petersburg by Andrei Bely
The Man Without Qualities by Robert Musil
The Man Who was Thursday by G.K. Chesterton
The Circus of Doctor Lao by Charles Finney
/hijack
Yes, I agree.
And (also in my opinion) the greatest detective story ever written comes in third place:
‘The Murder of Roger Ackroyd’ by Agatha Christie
Of the highest mountains on earth, which do you consider the highest? I’ll take Ulysses, Jeff 
Couple of unexpected things for me about it - the writing is timeless. Prior to picking it up I thought it might be more of an historic work - something to appreciate in context, trace its influence etc. No way. It’s like a Rembrandt painting.
The other thing is how human and warm it is when you boil it right down - definitely difficult in parts, but basically telling a simple story about people. Very different to some of his literary descendants.
Favourite novel is a different story - loved many of those mentioned already. Couple that I’ve not seen mentioned - I think Suttree is McCarthy’s best, not read too many books that pack such an emotional wallop. Put that one down in a daze.
And The Book of the New Sun by Gene Wolfe is a special book for me (and many others) - seems like a lot of talented SF writers put out consistently good stuff without ever really going deep and birthing a masterpiece. Maybe Wolfe had his mortgage paid off or something, because he bucked that trend and then some with this unique and fanastically ambitious novel.
Now I remember my favorite 20th C novel.
To Kill a Mockingbird
Black like me
The heart a lonely hunter
The Jungle
Are just a few for me.
Yeah my teen self would have agreed with you but as a 48 year old man I tried re-reading them and found them wanting. All this shows is that we mature and change.
I have given copies to both of my sons when they were about 12 and they loved them, we spoke about the concepts explored etc and in he end it got us talking.
Also this series got my Aspergers brother into reading, so yes although I don’t like them now they are very important to me and therefore a fave of mine.