It's the culture of an instance that makes the difference, not which software it runs, but there is often a correlation. Misskey tends to get more people who appreciate cute emoji and comfy vibes.

I prefer Misskey (Misskey fork at least) because it's just much more feature rich, Mastodon doesn't even have quotes, on the other hand Misskey has a lot of cool stuff like markdown, more customization, avatar decorations, emoji reactions etc But to each their own, from minuses Misskey has it's own API so the variety of apps is smaller compared to Mastodon

The main draw of Mastodon for me (and why I didn't stick with the *key servers) is following hashtags. Really eases post discovery in an algorithm free world.

Otherwise the misskey forks have all manner of neat features to make using them a delight.

I've never used Misskey but used various Misskey forks for about a year. I ended moving back to Mastodon. In my experience, the forks are very good at all the extra razzle dazzle they add (MFM, emoji reacts, drive, etc.) but often aren't as good at the basics. I'd pretty routinely have federation issues, missing posts from my TL, and posts that would just repeat endlessly in the TL until I reloaded the page. And those are problems I experienced on every fork I tried. I found that stuff more of a minor nuisance at first but it got pretty old over time. It's been a few months since I migrated back, so some or all of those issues could be fixed or improved by now too.

Also, app support isn't great. I think most of the forks implement basic Mastodon support now that will allow most apps to work. But the downside is you only get Mastodon functionality in those apps and not the extras.