Generally I see ReadMe's with games, particularly with plugins/mods, where they are used to provide instructions or various options. I'm not exactly sure why you would get a ReadMe with an ebook, but...
I would suggest looking through each ReadMe and saving any important ones (with instructions or options inside) after re-naming them to include the book (mod?) name (example: War and Peace ReadMe.txt). Generaly speaking you don't want a couple hundred files just named "ReadMe" lying around your hard drives - you will forget which ReadMe goes to which game/mod/book/whatever.
If these are ebook related ReadMe's, you could include the contents:
- into Calibre's comments field per book and then deleting the original file.
- into the ebook itself via the editor and/or Polish
Addendum:
This message was written with consideration for the
possibility that the original poster might be using calibre to organize material (music, etc) other than books where retaining a separate ReadMe file is still important.