How is the setting of American Gods significant to the overall meaning of the story?

This novel by Neil Gaiman, currently being produced as a TV mini-series, follows number of characters who interact with people who claim to be ancient gods. These gods have decided to try and resurrect their cults of worship in the United States, where, after centuries of displacement following immigration from Europe and elsewhere, their followers have largely forgotten them. The idea is that the gods were worshipped more enthusiastically in their native regions where their origins lie. And so the American setting of this novel becomes very significant.

The novel has been called a "road trip" novel since there is a great deal of traveling that occurs and important events that take place in these locations, all serving to advance the plot. The main character Shadow is released from prison and meets a man named Wednesday who invites him to work for him, and this involves travel from the start. There are a number of iconic American cities featured in the novel, like Los Angeles or Chicago, and the features specific to the cultures of these cities affect the things characters do there. Shadow is a mortal character who is chosen to help the gods bring about a kind of final battle for dominance within their pantheon. He hails from a small town in Indiana called Eagle Point, and this centrally located rural location is also significant. Indiana is a state located in what is known as America's "heartland"--a central region known for farming and agriculture, and its flat landscapes. The novel's plot takes Shadow to other places in the midwest, including locations in Illinois, Wisconsin and Kansas. Some of these locations are real, and some fictitious; and some of them have dramatic landscape features (like large rock outcroppings or lakes) that become associated with human sacrifices to the gods.