Let's consider some books. What category or genre they would fit in?
"Grapes of Wrath," by John Steinbeck
"Gone with the wind," by Margaret Mitchell
"Moby Dick," by Herman Melvill
"Call of the Wild," by Jack London
"To Kill a Mocking Bird," by Harper Lee
Each of these contain elements of one genre or another, suspense, mystery, adventure, action, romance, whatever. However, I don't think you can comfortably categorize any of them. They transend genre.
That, to me, is what makes a novel mainstream, and what makes it great.