Speaking as someone who ran a set of public forums back in the early days of the internet, the number one thing I can suggest is don’t do it alone.

Alone, you’re one person arguing with hundreds of other people that your opinion is the right one. This burns out anyone but the most narcissistic assholes (I should know, being the latter). With a team, you get to deflect attacks that would be personally directed at you to the overall team while relying on their support to provide a unified front. Bullies generally target single individuals - they rarely go after groups.

This can be hard to build, and it often relies on a third party in the admin role to encourage the creation and unity of the mod team until it gets on its feet, often becoming part of the team in the early phases until it runs well on its own. A minimum of three people is usually what it takes to really make a community thrive cleanly.

Unfortunately, the fragmented nature of the Fediverse makes it difficult to build these kind of teams, as the mods have to be users on the same instance platform, and a small instance with only 20 users can end up with an enormous amount of content and commentary from users across the wider Fediverse. This, of course, ties into @hoodlem 's comment regarding bandwidth costs for instance owners - the speed at which your traffic can scale is exponential, and you need to be prepared for it from both a financial and staffing standpoint.

One solutions that could help would be to have an ActivityPub login standard that would allow logged-in users from one instance to moderate a community on another when given permissions. A cross-platform private messaging standard would help here as well. Of course, both of these functions would have to be encrypted and secured to prevent cross-site attacks, but they could be steps in unifying the Fediverse without centralizing it.

EDIT: as pointed out in the comments, you can mod across instances, but it doesn’t look like you can mod across platforms yet.