There are some very good questions here on SO about file management and storing within a large project.
Storing Images in DB - Yea or Nay?
Would
In order to avoid creating an excessive number of entries in a single directory, you may want to base creating directories on pieces of the filename. So for instance, if you have a file named d7f5ae9b7c5a.png, you may want to store it in media/d7/f5/d7f5ae9b7c5a.png. If your filenames are all hexadecimal then this will restrict the number of entries in a single directory to 256 up until the final level.