I mostly run the official adventures set in the Forgotten Realms with minimal changes; however, a few years back I did run an episodic campaign set in a homebrew world that had a mashup of ideas from various places.
The most notable thing that I thought was cool about it were the religious beliefs of the various races/cultures. To start with, I borrowed heavily from Game of Thrones and went with the whole "old gods and the new", with primal nature deities still worshipped in secret by rural folk and druids and the like, and a more organised religion (the Andarian Septry) based around a single god with seven aspects (Father, Mother, Maiden, etc). I went with an Eberron approach and made it so no one knew if the gods were real or not, but I took it a step further by removing divine magic (and clerics and paladins) all together.
For the dwarves, I borrowed heavily from Dragon Age. So my dwarves didn't worship gods. Instead, they honored the "best and brightest" among them as saint-like paragons. They also revered a Mother Earth-like entity they called the Stone.
Halflings, meanwhile, worshipped a trio of female deities they refer to collectively as the Sisterhood. One of them was their goddess of luck, and they only ever refer to her as "the Lady" because to say her name is to invite misfortune.
As I said, that was the thing I thought was the coolest, but unfortunately my players didn't really engage with that aspect of the game, so none of those ideas really saw much use in actual play.