Regional divisions are present in countries all over the world. Most are accompanied by ethnic and linguistic differences. Belgium has French speaking Walloons, and the Dutch speaking Flemish. Canada is divided between French Canada and English speaking Canada. Nigeria has a variety of ethno-linguistic divides.
This is not so in the United States. The most fundamental regional division in the United States is the one that gave rise to the American Civil War between former Confederate States, the border states, and those states that remained in the Union.
The Civil War divides remains relevant today. There is a greater cultural divide between Richmond, Virginia and Philadelphia, Pennsylvania, than there is between Boston, Massachusetts, and Seattle, Washington. Columbus, Ohio has more in common culturally with Des Moines, Iowa, than it does with Louisville, Kentucky. The dialect of Los Angeles is closer to that of Cincinnati, than it is to Nashville. Residents of Phoenix, Arizona or Los Alamos, New Mexico do not sound like those from Dallas, Texas or San Antonio, Texas.
While the United States has Native American, Dutch, Spanish, French and British roots, those are not the fundamental divides of American culture. Both the Puerto Rican and Dominican populations centered in New York City, and the Cuban population centered in Florida, are largely a result of post-colonial era immigration, not holdovers from Spanish colonies. There are very few American remnants of the French presence in North America outside of Louisiana. Most Native American populations in the Eastern United States were either obliterated to the point where they had no tribal identity, or exiled to Western reservations. There are cultural anthropologists who claim that there was a significant Native American impact on American culture, but even then largely place the point of transmission deep in American history during the pre-revolutionary period.
The Spanish presence of in the Southwest had a greater residual impact. But, that impact was largely confined to California, Arizona, New Mexico, Southern Colorado and Texas. Moreover, immigration from the eastern United States has overwhelmed the historic culture to a great extent. The burrito popularized in Denver by the chain Chipotle, and its imitators, came to Colorado (and much of the rest of the United States) not via New Mexico or Texas, but through San Francisco. Arizona is known as much for its snow bird retirement communities, as its Spanish institutions.
Immigration naysayers notwithstanding, there has never been a major successionist movement in the Southwest. California and Texas were both Mexican territories colonized by English speakers that broke away from Mexico, not the other way around (Hawaii's legacy is similar, although, it was its own kingdom, rather than a Mexican territory, prior to English speaking colonization). Almost all non-English speaking communities that have contributed to the American melting pot have largely assimilated within a generation or two. There is strong evidence that this trend continues in existing immigrant communities. While more than one language has been spoken in the United States for most of its history in certain places at certain times, it has not sustained dominant non-English speaking communities outside Louisiana and Navajo Indian Reservations. Even there, the difference have been greatly diluted, English is widely understood in those areas.
Also, the cultural divide between the North and the South in the United States mostly pre-dates the waves of European immigration that surged into the Northern States from Germany, Italy and Ireland, although there was a considerably Dutch presence in New York and a "Pennsylvania Dutch" presence in the North. But, a considerably number of Irish immigrants made their way to the South, so it was not entirely insulated from European immigration either.
The divide between the North and the South in the United States on a wide variety of political, foreign policy and social issues was in place before the Revolutionary War that began in 1776, and has remained remarkably stable since then.
The culture divide between the North and the South in the United States even pre-dates the religious divide between the two regions that now is a major factor sustaining the separate regional identities. The South was the more secular part of English speaking North America until the 1840s when the Second Great Awakening transformed it with a form of conservative Christianity that still flourishes today.
The most obvious answer is the institution of Southern style slavery, different in character from most slavery and serfdom regimes that had preceded it, created the cultural differences that survive today between the American South and the rest of the country. Without those cultural differences, there likely would not have been a Second Great Awakening, and immigration from Europe would not have been so intensely a Northern phenomena. The institution of slavery was such a powerful cultural force that it almost overwhelmed commonalities of a common English linguistic, cultural and legal heritage, and a common revolutionary war experience.
Some of that change was likely a product of the institution of slavery itself, and some of that change was likely a product of unacknowledged cultural borrowing from the Africans brought to America, with a light sprinkling of local Native American cultural borrowing before they were exiled (the Native American tribes of the Southern U.S. were considered by English settlers to be among the most "civilized" in the Americas and thus there was less hostility towards borrowing from them culturally). How much each component contributed is hard to ascertain.
Also, many of the socio-economic indicators that divide the North and the South have a much larger racial component that most people acknowledge. The South does less well on most socio-economic indicators than the North. But, while that distinction crosses racial lines, many of the statistical differences between North and South are attributable more to large divides between blacks and whites generally in the United States, and to the much larger percentage of the population that is black in the South than in the North, than to those across the board differences.
Both the difference across racial lines, which are attributable to a great extent to a historically more agricultural economy, and between races across the United States, which are attributable to a great extent to a legacy first of slavery until the end of the Civil War, and then to legal or legally accepted segregation practices for another century, flow from America's history of slavery.
Many liberal legal scholars have argued that affirmative action and a variety of other remedial and social equality measures are justified by the 13th Amendment to the United States Constitution, because the status quo is a legacy of slavery. I'm not sure that this is a great argument. It proves too much. In a sense, the very regional divide that made the United States a federal country is also a legacy of slavery, but the 13th Amendment clearly wasn't designed to dismantle that overarching constitutional architecture.
But, on the other hand, in a larger sense, I think that those who see the issue that way are correct in believing that until the cultural remnants of the institution of slavery have been dissolved, that we have not really fully moved on from that shameful part of our history.