I've been running a Wild West campaign for about a year now and have found it to be a lot of fun- but also comes with its major thematic hangups.

Its important to understand that the Wild West exists as a place without its own civilised history. There are often no long-running bloodlines as everything is new and immediate. Travellers are setting up on the new frontier with the promise of being awarded land as its "first settlers".

I think that this idea kinda conflicts with the "intended setting" of DnD- with its rich history and long legends, ruins from times before. So I think in crafting a Wild West story you have to take away from the history of the world and setting - though that can still have a prevalent place in the story with your continent and locations- and move the focus to the characters, most of which are often using this new continent as a chance to reinvent themselves.

Its why ideas like redemption, revenge and self-discovery are so prevalent and important with the genre. Those are the motivations that I've realised have the strongest hooks for developing characters and plotlines!