Generally speaking, "%appdata%\Spore". I recommend backing up the ENTIRE folder.


More specifically:
"Spore\Games" contains game saves and galaxy data.

"Spore\MVJCache" contains the image cache of your in-game Sporepedia. I'm not going to pretend I know everything that means, but I'm almost certain that it at least contains data on all your unpublished creations, if not more. I'm almost certain it's more important than I've commonly read online regarding backups. I've read it might cause issues with the game recognizing your creations in the Sporepedia if you delete it. It's mostly an inconvenience more than anything, it won't categorize them properly or show them properly, but you're still able to access them.

The "Pollination.package" is important if you want your saved games to be identical to before. Otherwise it will be regenerated differently, and npcs, buildings, vehicles, and plants may generate differently.
You can exclude, delete, or remove (probably back up though just in case) your "Pollination.package" if you want to purposefully regenerate it. You can read up on what it does and how it works here: https://spore.fandom.com/wiki/Pollinated_content

"%userprofile%\Documents\My Spore Creations" contains your... creations.
Your published creations SHOULD automatically be backed up to your Spore Account on EA's servers. If you have one. (I don't know if there are any exceptions.) Nonpublished creations are NOT saved to the server, and therefore are completely local to your device.
(Planets and game save data are also completely locally stored.)

Back it up anyway if you want to be safe.

Just backup the entire "%appdata%\Spore" folder. Better safe than sorry.

Interestingly though, despite it being stored in the C: drive (Or whatever drive your %appdata% is in by default) so it shouldn't be affected by just reinstalling the game to a different drive... Some of my saved data is missing, notably my saved games, but also the game doesn't recognize that I've played all the stages so I can't start in any of the stages other than cell or space. I'm in the process of figuring this out. (I haven't played the game in years so I don't know if it was an issue before I returned too or what.)