I would love to answer Americana by Don Delillo because the title alone would nail the OP but sadly I can’t.
I will nominate one of his later novels, White Noise.
How much of it happened? An update on this what if book for 2017 would be great.
Red Sky at Morning by Richard Bradford
I’ve already given my favorite, but a couple of others:
The Screaming Mimi by Fredric Brown – Brown wrote some great mysteries (in addition to science fiction, fantasy, and thrillers). I’d include several (The Fabulous Clipjoint arguably being the best of these), but this one is one of my faves. Well-written, bizarre turns of plot. It feels as if Robert Bloch cribbed fro it for Psycho.
A lot of Robert Heinlein. It’s hard to choose which, especially out of the juveniles, but I’d give "favorite’ status to The Moon is a Harsh Mistress and Double Star.
I could have chosen this just as easily. I would read Helprin’s daily to-do list, he is that good a writer (although other novels of his didn’t quite hit me like ‘Soldier’ did).
mmm
I hear “favorite American novel” and to me the phrase suggests that the answer needs to be a novel that is essentially “American” in fundamental ways – in other words, not just my favorite novel written by an American.
So my favorite American novel, as I read the question, is a novel that is in so many ways about and representative of the American spirit and character. It tackles race, sex, religion, capitalism, and exploration. It is both intensely optimistic and deeply pessimistic. The book itself is a total shambles, but I can’t help forgiving its many faults and failures because of its reckless artistic ambition and fundamental kindness of spirit.
Can you guess the book I’m thinking of? It’s Moby-Motherfucking-Dick – although if I were in a more pessimistic mood, and looser about what constitutes a “novel,” I might’ve gone with Armies of the Night, the “non-fiction novel” by Norman Mailer.
Seconded. I’ve lost count of the number of times I’ve read it.
The Long Winter by Laura Ingles Wilder. Oh, to be able to go back to the days when I loved reading fiction so much!
**The Book of the New Sun **by Gene Wolfe
Bones of the Moon by Jonathan Carroll
Hey, you posted for me. Exactly my feeling.
Lonesome Dove by Larry McMurtry
My intention was to ask for your favorite novel by an American.
mmm
Revolutionary Road… the failure of promises, psychological breaking, and the myth of the American Dream.
Cryptonomicon.
(Sadly, the last good book Stephenson wrote.)
Slaughterhouse-Five.
If you’re flexible about allowing 4-5 separately bound objects as a single book.
My favorite is Moby Dick, although I think that *The Great Gatsby *and Huckleberry Finn are also fine choices.
The Great Gatsby is nearly perfect, but I also like Angle of Repose by Wallace Stegner a lot.
Oh man, Frank and April Wheeler, what a couple. In a similar vein (and choosing despite the OP’s admonition to stick to the American-themed), The Man in the Gray Flannel Suit by Sloan Wilson would be a good book to pair with Revolutionary Road.
Damn he could write. Love Crossing to Safety, too.
But yeah, Gatsby.
If it’s the book I’ve read the most, it’s Dune. I’m cool with that, too. 
The OP only asked for an American novel, not an American-themed novel; and he further clarified in Post #32 that this means a novel by an American.
Personally, I’m not sure what my answer would be—I suck at “What’s your favorite…?” questions where there are huge numbers of possible responses—but if I thought about it enough, it might even turn out to be the same one mentioned in the OP.
In that case, I’ll go with Colson Whitehead’s The Inuitionist, which is tightly focused on just a few aspects of the American Experience: what is it like to be a female African-American elevator inspector, in a world where elevator inspection is taken very seriously?
I’m very fond of this novel because, while working in a bookstore, I managed to sell a copy to an elevator inspector who was inspecting our elevator.