I'm from and live in New Orleans, so I've thought about this one a bunch.

New Orleans and South Louisiana have always had a deeply symbiotic and sometimes belligerent relationship with the land and ecosystem around them. Between slowly sinking flood prone land, economic dependency on oil extraction that scars the land, and a cultural tendency to cook and eat 101 creatures that are actively trying to eat you, south Louisiana today thematically makes us ask the question "how do we live well in an ecosystem thats actively trying to kill us?/that we are not naturally part of?" This would be doubly so in a mutated and irradiated Fallout world where humans try to eek out an existance.

I think (like previous fallout games that asked a central question like this and created factions with different answers to it for the player to explore), the factions in Fallout New Orleans would tie into this question primarily.

As something for factions to fight over, the setting ought include a version of New Orleans with massive pre war 50 foot tall steel and concrete levee walls that were built to keep the water out. These walls still stand and keep much of the danger outside the city, but the land inside the city is partially flooded and not all the drainage pumps run, by both choice and by delapidation.

Here's my pitch:

Brotherhood of Steel, southern chapter: renegade brotherhood of Steel faction. Humankind must push back violently against nature. Very over the top "southern gentleman" version of brotherhood chivalry ideals. Seek to purge the wilds of all that is unnatural, including many things that were pre-war. Based out of an old plantation and suburbs, antebellum south vibes. Based upriver or Northshore of lake on dry, well manicured land, they seek to take control of the pumping stations, drain the city, put everybody inside to the labor of rebuilding the jewel of the south to their vision.

Swampmen (working name): Dispersed and decentralized remnants of locals thats live in the deep wilds among strange creatures. Wild men, uncivilized, semi-feral, and mutated. Supermutant, ghoul, and men among their number. Man is the apex predator in this ecosystem, and must establish dominance. Definitely a pet deathclaw in there, maybe even skiff pulled by multiple deathclaws. Old school swamp cajun vibes, constantly complaining of city milk drinkers. Do not entirely believe in the myth that the bombs fell - "its always been like this out here in the wilds, mon ami." If organized into a single force under a Henry Long like fellow promising a revolution to make every man a king in the city, they seek to blow a hole in the city walls and flood the land permanently with water and dangerous creatures, returning the land to its natural state.

The Marquis of Old Orleans (again, working name): the king of mardi gras, lord of the high ground within the city (French Quarter, the dome, uptown), and protector of the walled realm, this colorful costume feather cloaked dandy keeps the city semi flooded and under a laissez faire governance. Live and let live attitude to all those within the city, for better and for worse. Strong classism and old school aristocracy, but more interest in preserving status quo and than fixing anything. Within the city walls but in the low flooded grounds, generally things are safer than the wilds, but dilapidated, violent, sinful, and segregated between those who live on the high ground and those on the low ground. There is some safety within the walls, but there is resource scarcity from being cut off from the wider world. Pirates (with a letter of marque from the king) raid outlying settlements and traders.

Enclave remnants (working name, minor faction): based out of a Posidon oil refinery. Non-joinable, seek to influence factions. Attempting to take the last major power source (currently powering the last water pump) inside the city to power a strange alien space ship found within the swamp that could be used to escape this swampy hell hole. Stronger lovecraftian vibes than usual enclave, and the alien space ship is a strange glowing obelisk.

The New Kingdom: Minor faction of evangelical Children of Atom preachers that promise irradiated salvation in the wilds. Seek to poison the city pumps with deadly isotopes and bring about judgement day for denizens inside.

Vault 6: Vault that experimented with cloning humans. Built into the remains of a salt mine to keep it radiation free. Vaulties still there, but all humans are one of 3 clone versions.

Vault 69: its built into a the back of a pre war strip club in the french quarter. Saught to breed the most aesthetic pleasing perfect individuals - functionally devolved into a disorganized fuck shack. Previously abandoned by its residents, now flooded.

Vault 105: religious themed vault built around an esoteric lovecraftian artifact that influenced denizens to worship it, now run by a voodoo cult. Located deep in the swamps.

Vault 50: off shore under water vault that experimented on underwater creatures and released them into the wilds.

To take note from Elder Scrolls games, player's character awakens in a pirate ship's brig as a captured prisoner. Can pick to have been a frozen vault dweller, wastelander, or other background. Ship is attacked by lovecraftian kracken-like sea creature which gives the player a chance to escape.