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.