I'd say that my first mistake I made when I started making campaign settings of my own was just... "trying to be too clever". I didn't realize what made the adventures I liked to run (Like Keep on the Borderlands and Isle of Dread) fun. I put in a lot, really too much, work on setting details, plots going on, backstory and history... And it just wouldn't come up in game or players wouldn't be interested in it, and I'd be ticked at all the wasted time and sometimes try to force the story that I wanted to tell on the game, despite them, because I had put in all that work.

The other problem was just not allowing simple archetypes to be believable (At least simple archetypes as the system had established) and trying to kitbash it into something the system wasn't really meant for.

My first real success is when I finally did just kind of sit down, shut up, and make a "simple" campaign setting in a Robotech RPG. Fleshed out a zone based off New Seattle Settlement for the third invid war. Put up typical encounter zones, made sure all the book stuff could be used, and just put down some random interesting NPCs and simple, easily mutable plot hooks and not much else. Worked like a charm. And that setting just reminded me of what I now hold as a truism of setting crafting and adventure plotting. Just keep it simple. Focus on making good, solid contact rather than going swinging for the fences, and it works out so much better.

At least it works for me that way. More clever people than I would probably be able to pull off the home runs easier.