I think with big libraries, the biggest problem would be in the initial upload of files (assuming they all went in at once) along with organization. Indexing is intensive for the battery and probably the resources for the Kindle and it will go to work indexing everything if it is all uploaded at once. You'd want to keep the Kindle plugged in (USB or charger) during that phase.
Organization may be a problem just because you would end up with pages and pages of books with a large library although collections would help to some extent. I'd probably be tempted to sort everything alphabetically, but that might make a mess of the home screen since all books get shown even when they are in collections.
The solution then becomes to name your collections with special characters at the start so that they sort at the front... There are a few threads with regard to that. That is one aspect I hope Amazon improves with future firmware. It will be nice to sort things cleaner, to nest collections, and to keep books out of the home menu no matter how you sort things. I also think it would be nice to have the ability to toggle a visible tag (like the "new" one that shows up on uploads) so that you can keep track of what you are reading easily.
I have made suggestions like this to Amazon as part of their request for feedback.
Last edited by emalvick; 10-21-2010 at 11:38 AM.