The first campaign I ran was fairly standard in D&D terms, with one major exception.
The main conceit of was that the world was completely flooded for 500 years. If your first thought was a reference to Waterworld, know that you are exactly like everyone else who has ever heard me mention this. I had some fun figuring out the natural consequences of "exactly like a standard D&D campaign, except it was flooded 500 years ago".
Humans moved to ships and a single large floating island called Shell (so named because it was once the shell of a giant turtle, floating inexplicably).
Elves manipulated mangrove trees into living tree-boats called mangals (it was handy that English already had a word for "mangrove swamp", which I simply coöpted), the largest of which is the size of large cities after 500 years.
Gnomes and dwarves teamed up, built a fleet of submarines, and have since interbred into a single species, called engineers. Seaforged (created by the engineers) are like Warforged, but created to function at the bottom of the ocean.
The half-ogre pirate king Gus Dreadworm, after a long and successful career, moored his fleet together and retired. More and more people moored their decaying and crumbling ships (mind, aside from the elven fleets and a handful of trees on Shell, there are very few trees to repair ships with) to Dreadworm's fleet until it was more properly a floating city (explicitly a ripoff of Armada), known as the Disreputable City.
The drow prayed to Lolth, and, with her help, the most powerful drow spellcasters decanted their entire civilization from the Underdark to the Deathly Plane of Shadow (I'm using a simplified set of six elemental planes that do double duty, filling the rôles of the outer planes).
The mind flayers discovered that tritons were almost as good as humans and elves for ceremorphosis, allowing mind flayers to survive underwater.
The rest of the humans, elves, dwarves, gnomes, orcs, kobolds, goblinoids, etc, wound up either interbreeding with one another or dying out, to the point that mongrelfolk are among the most populous races.
This has natural game consequences. For one thing, any campaign set in this world is likely to be largely aquatic, so Stormwrack is in order.
Aside from the commonness of mongrelfolk and the rarity of orcs, halflings, dwarves, and gnomes, some of the remaining races are altered. I'll dedicate a later post to combining gnomes and dwarves into the engineers, but I'll briefly cover the minor changes here.
Because the culture of the elves is so focused around maintaining the mangals, their Favored Class is now Druid.
Seaforged contain no wood, so they are no longer susceptible to spells that target wood. They do, however, contain materials like whalebone and coral, so they are susceptible to spells that target bone or coral. They're created to function at the bottom of the ocean, so they have darkvision. They're created for mining on the bottom of the ocean, so they have a racial penalty of -4 to Swim checks.
Drow are now native to the Deathly Plane of Shadow and gain the (Extraplanar) subtype if they travel to the Material Plane. (A game using standard cosmology might move them to Lolth's plane of the Abyss, or else someplace like Carceri, the Gray Waste, or Gehenna.)
A mind flayer tadpole applied to a human, elf, or mongrelfolk becomes a mind flayer. A tadpole applied to an engineer becomes a Small mind flayer (as if naturally under the effects of a Reduce Person spell). A mind flayer tadpole applied to a triton becomes a mind flayer with the (Aquatic) subtype. Any other combination uses the half-illithid template.