Really interesting set of questions!
One challenge I see in running a unique setting is establishing expectations regarding how the world will function, so that everyone at the table feels they can interact with the world and have an understanding of what is likely to happen when they do.
An easy way to address that is to build the world collaboratively with your players. A natural result of the process is that everyone is more or less on the same page. There are lots of methods for this in a range of games. @yochaigal wrote a particularly good set of procedures: Build Your World
If you’re not into collaborative worldbuilding - I would just say being as clear as possible about the cores ‘rules of the world’ is the most important element. As @VanWinkle said, a lot of (all?) unique settings draw from established sources, so giving your players references to your own inspirations can be helpful.
Regarding visuals, I’m also not an artist, and I find combing public domain images to be a great way to gather images - see some great sources for this just posted over here: Design Resources
Combing Pinterest and building a mood board is also a good move 
A mood board for my sci-fi campaign