I've been thinking about this recently myself and also used email as my go-to example -- and it's not lost on me that, if Mastodon really follows that path, we're likely to end up with a few immense instances that provide added services, either in exchange for a small fee or for ads (or, let's be honest, through data mining).
I suspect one of the biggest potential places for improvement will be providing a semi-formal process around moderation. The current approach presents itself as a kind of socialist/libertarian communal utopia, and it can be depending on how a given instance is run -- but in practice, each instance is a monarchy with absolute power over not only your presence in the kingdom but which other kingdoms you're allowed to talk to. Your social graph can be broken at any point because your admin has decided, for any reason, to stop federating with an instance you have followers on, or vice-versa. The net effect is that you can be punished for transgressions, real or imagined, that you weren't a party to (and might not even be aware of). And I don't think that has a technical solution, just a policy one.
Of course, it's possible that Mastodon -- or, more likely, a future similar network, maybe one built on ActivityPub, too, so it could federate with Mastodon servers transparently -- will solve this by requiring instances to agree to slightly more formal policies around federation and moderation: here is disallowed content, this is the reporting process, this is the appeals process, etc. This can absolutely be done; it was done, three decades or so ago, back in the days of FidoNet. But I suspect the folks most enthusiastic about Mastodon as it exists now would find that anathema.