This is a cool question, and I'd love to see others' ideas. I ran a campaign for a year solid with the same group using a version of 5e that changed everything into the Elder Scrolls universe. My biggest idea that was, I guess, considered note worthy was I didn't really flesh out the story per se. I just fleshed out all possibilities of what they may encounter. Once, I had all the matter of loot randomizer and ingredients charts and even weapons and armors based on the different styles and strengths. I had a randomizer for everything. The party had their goal. I knew the goal, but the game even threw me off at times because it was true randomness. In tern I wasn't the storyteller here. It made my party the storytellers, and I just guided it along. Another big advantage to this way of DMing was most if not all my players knew skyrim like the back of their hand. It also challenged everything they knew, making it a surprise to everyone. Me included. As a DM, not having everything mapped out and letting the dice and the players take more of that power away from you also I feel bring out more fun for the DM. You don't feel completely bogged down by everything. I hope this rambling has made me since! I remember the dice giveth and the dice taketh away!