Only experience can tell you that, I'm afraid, since your use case will be different than mine and others.
To give you an example, I use multiple browsers at once for different purposes. Each browser has its own bookmarks, extensions, site settings and other configurations. Having to set it up every time I re-install the OS is a bit of a pain because it takes time.
So, I simply copy the profile folders and drop them in the new OS, and it's as if nothing ever happened. Well, currently I have my drive partitioned with a dedicated /home partition, so I don't need to do this anymore. But you get the idea.
Another example might be custom fonts that you may have downloaded, or things like the bookmarks from the file manager:
In short, anything that has a "Export to..." option in the menu bar and that you think might be worth keeping around.
But don't over think this too much. All of this can always be re-configured as needed, it's just a convenience. Perhaps the most important thing to back up are actually the bookmarks because those are tough to remember, especially when you have dozens or hundreds...