I like "different" settings. I've been a bit bored with the "standard" setup for decades now.
That said, it's tough to do creative campaigns because it requires a lot of work by the players. To understand how to roleplay in a different culture, you have to understand the culture, and gaining that understanding is a lot of work. Sure you could roleplay pseudo-middle ages European characters in a land with Mayan architecture and a few different monsters, but what's the point? It still mostly the same old same-old. I think what you need are players who are interested in this type of experience and willing to put in the effort to make it work properly.
I did have one real success along these lines. I wanted a change of pace, so I decided to set a series of adventure in a previously unexplored part of my world with a culture primarily based on that of the Philippines. I felt I could carry this off because I spent a couple of years in the Philippines as a missionary and understood the people and culture quite well.
To start things off, the party was ambushed by slavers while they were on their way back from a dungeon, hit points and spells depleted. The adventure really started when they excaped from the slavers without their gear in the middle of a hostile jungle. In retrospect, I can see that I was lucky; this could have gone quite badly. I should have discussed the change in direction with the players first. Fortunately all the players had a blast and things worked out. Anyway about 20 sessions of play occured in this land, many of them very RP heavy. Eventually, the party worked its way to the coast, recovered most of their gear, avenged themselves on their enemies, and went home. All good fun.
About a year later we started "the Southern campaign" with characters native to this area. It worked because everyone understood the culture, history, and myths of the area.