Mailing List Application?

If you are already subscribed to hundreds of mailing lists, it is probably too late, but the common sense thing to do would be to use different email accounts. You could even have one email address redirect email to the other, where it automatically gets sorted. Gmail allows you to use aliases with the same email account.

Another thing you could do is use RSS Feeds instead, when they are available. I use Outlook, which includes an RSS reader.

Thunderbird as email client has the feature of Saved Search folders, that operate as virtual folders. Search folders can be attached anywhere in the real mailbox hierarchy, so can be nicely organized. This lets you leave all your email in one mailbox that is only virtually divided into folders.

See this article : How to Organize Mail Flexibly Using Virtual Folders in Mozilla Thunderbird.

To add a similar structure to Gmail, see Adding Persistent Searches to Gmail. This uses the Greasemonkey Firefox extension together with this user script. It adds a "Searches" box on the left side, below the "Labels" and "Invite a friend" ones, where clicking on a search executes the saved query. However, this is not as flexible a solution as when using Thunderbird.