There are several settings in American Gods, and they join together to make a statement about the message of the largest story arc in the book, that of how American culture has evolved in terms of values, ethics, and beliefs. The modern highways, towns, and landmarks of the broad United States landscape is the primary setting, and the secondary settings are in other countries, depicted in flashbacks, in various past centuries.
One of the primary themes of the book is an exploration of how people's world views, ethics, and priorities are shaped by their belief in, and relationship with, "God," or "the Divine." Interestingly, Gaiman lists not only deities from various religious pantheons in his story, but he also incorporates social constructs and inventions into the concept of "God," thus including "Mr. Town," "Mr. World," and "Media," to name a few. This implies that "Gods" are whatever people give their time, energy, and attention, and that Gods can be created by people.
By using a large swath of the United States as his primary setting, the author is clearly making a statement that his novel's themes apply to the entire USA, and not just to the specific towns and landscapes that are described in the book. The winding, repetitive road trip taken by Shadow Moon and Mr. Wednesday is a symbolic "tying together" of all cultures and subcultures in the United States. This is underlined by the mention of "the center of the United States," which was called, "Humansville, Missouri," and was considered by the Gods to be "a neutral place."
"As near as anyone could figure it out, the exact center of the continental United States was several miles from Lebanon, Kansas, on Johnny Grib's hog farm. By the 1930's the people of Lebanon were all ready to put a monument up in the middle of the hog farm, but Johnny Grib said that he didn't want millions of tourists coming in and tramping all over and upsetting the hogs, so they put the monument to the geographical center of the United States two miles north of the town. They built a park, and a stone monument to go in the park, and a brass plaque on the monument. They blacktopped the road from the town, and, certain of the flux of tourists waiting to arrive, they even built a motel by the monument." (Pp. 426-427)
The war between the Old Gods, which include Kali Ma, Odin, Anansi, Czernobog, Lugh (Mad Sweeney), Thoth (Mr. Ibis), and others, and the "new gods," Media, Town, World, etc. demonstrates that the whole of the country, though we brought ancestral Gods and Goddesses with us when we emigrated generations ago, has adopted new ideas, priorities, beliefs, and ethics, threatening to leave behind even the memory of the ancestral Gods we once worshiped, and their value systems. It also makes a statement about the nature of the Divine, implying that the Divine needs us, not the other way around, for the humans in the novel can and do create their own Gods, shaping them, feeding them, and even evolving them.
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.
https://arteriesofamerica.com/2011/07/04/american-gods-roadtrip/