Zelda rpg
Pardon my two cents on the matter, as this pitch did rather grab my attention.
1) Given the overall nature of BoTW's story and how it relegated all the previously-existing lore from older games to various retellings of legends, a deep understanding of LoZ's lore wouldn't be mandatory. It would certainly help enrich the game, but it's not required for players since they would reasonably be playing characters who have grown up in a post-Hyrule world.
2) For the sake of simplicity, I feel D&D 5e would be an excellent fit for BoTW. It is a very low-threshold system that is easy for new players to understand, and it has a lot of room for customization. However, since BoTW is a rather low-magic setting (where characters other than Link, Zelda, and Ganon are concerned), it would perhaps require some tweaking to give mundane explanations for otherwise supernatural elements. Sheikah technology would certainly be a reasonable stand-in for magic in many cases.
3) I would personally set the game a few years after Calamity Ganon's final defeat, where both Link and Zelda roam the land to establish a new Hyrule. This would allow players to be aware of the events of the game and help in rebuilding a new kingdom, which offers a more hopeful tone than if there was still Calamity Ganon looming on the horizon all the time. The players wouldn't necessarily ever need to directly interact with Link or Zelda either - just having them being a known force in the land would be enough. Further, all the other normal threats (roaming Guardians, bands of monsters, environmental hazards, etc) would all still be in effect to challenge the players.