Maud reminds me that yesterday was the 80th anniversary of the publication of The Great Gatsby. When I think about the Great American Novel, this is the one that I think fits that description most.
Why? Because it's the classic story of reinvention, of money and glamour, and failure: the things that epitomize the American experience. Yes, there's Moby Dick, which plays to our obsessive nature and the ruggedness that built the country. There are probably others that could contend for the title, but The Great Gatsby is It. So there.