Salinas Valley, California
Yes, yes—we know that the first part of the novel takes place in Connecticut, but that's largely just setting the stage for when the action moves to the Eden of the story, i.e. that Paradise that is the California Central Valley.
Historically, when the United States was being settled in the nineteenth century, California was seen as the endpoint to Manifest Destiny, which was the idea that God had decreed that the United States would span from coast to coast on the continent. So California has a history of being a kind of Promised Land for Americans. The fact that this area of the country is known for producing tons of produce also helps give it an Eden-esque flavor, so it's an appropriate place to set a re-telling of Genesis.
If you haven't already, now might be a good time to take a look at our discussion of the Garden of Eden in the "Symbols" section get a clearer understanding of its relevance to the story this book tells (or re-tells, and then re-tells some more). There's also some good stuff in the "Themes" and "What's Up With the Title?" sections, if you want to peek around a bit. We're happy to wait.
Okay, ready? Onward.
Aficionados of John Steinbeck won't see anything weird about East of Eden's setting. Steinbeck grew up in Salinas (as we see in the novel itself) and pretty much everything he wrote takes place in the Central Valley: The Grapes of Wrath, Of Mice and Men, Cannery Row… the man doesn't exactly venture far from home. But hey—they do say to write about what you know.