I can tell you how I do it, but there may be a better more efficient way.
When I have finished a book, I highlight it in calibre and then I click on the metadata button at the top. Under 'tags' I have a 'Read' category and add that to the metadata for the book.
When I go to add books to my reader, I click on the tags button in the lower right corner. In the left pane that opens, I can sort my books by removing those I have already read from the list. So I might choose to remove the all books from the list that I have already read, then ask it to list only science fiction or children's books. I can then highlight those and send to device.
Calibre will use the tags to create folders on your reader. So when I go to Collections on my 505 there will be a folder for my science fiction books and a folder containing the children's books.