This page lists the changes to D&D 5th edition in order to run a Touhou Project game.
Flying: In Gensokyo, almost everyone outside of mundane humans exhibits the ability to fly. As a result, there are several options for the DM:
Note that, while characters do have the ability to fly, it's typically not used outside of a fight, or when speed is needed. Another solution is to discourage having it be used by limiting it to a total of 1 hour of flight per long rest.
Skill Proficencies: Skills may be used for slightly different things than they are in basic D&D. Nature is used for knowledge about different creatures, as usual, and history can also be used in some cases, as most creatures are based off those from old stories.
There's also a new skill added, Intelligence (Science). This is used to understand modern technology, as well as that of the Lunarians.
Added Races: New races are available to player characters.
Added Backgrounds: Player characters have a modified selection of backgrounds to choose from.
Dueling Rules: Modern Gensokyo uses a system of dueling in order to non-lethally resolve disputes. Old Gensokyo does not.
Added Creatures: Many new creatures are added. Of note, many of these are named, unique characters.
The World of Gensokyo: Touhou Project is set in Gensokyo, a land based off Asian mythology, an entire world created to preserve they dying creatures of fantasy.