I think the thing I dislike about Mastodon the most is kind of a core part of the federation:
There are so many times I end up on a toot page on some instance that's not my primary instance, and I go to 'retoot' (boost) the thing, then up pops the whole "you have to copy this address, go to your instance, paste it in search, then you can retoot it there" schpiel
Too much cognitive overhead, and the workflow is terrible on touchscreen, so I just don't do it.
Centralization would solve it... but then that's kind of antithetical to the whole fediverse.
Also I remember there's a Mac client for Mastodon now (Ivory for Mac), need to try it out.