They are typically temporary files and folders that some poorly designed installer/uninstaller failed to remove. What I do with files and folders I am not sure are safe to delete is simply rename them by tacking the word, "delete" and today's date at the end of the file/folder name.
This will, in effect, make the file/folder unavailable to Windows and/or the program that created it.
Then I will simply use the computer again and see if I broke something.
If something does break, I simply remove the delete and date and I'm back in business. But typically, I totally forget about it, then months later, I stumble on it again, I can check the date and determine if safe to delete. By just adding the word delete and the date (instead of totally renaming the file/folder) I don't have to worry about remembering the original name.
As far as not being able to delete, you may have to do it (renaming too) in Safe Mode - or get radical and use
MoveOnBoot which will tag the file/folder for deletion early in the next boot process, before any program can get its hooks in it.