You might want to try a program like MailWasher, which allows you to view all of our mail in a text only format (many spam emails contain links to graphics and when you download them, again, it knows that the account is active) and then add them to a safe list or delete them and all before you download them.
You can also mimic a bounce - which makes it look to the sender as though the account doesn't exist (however, since most accounts sending spam aren't real, this isn't normally that great).
What you can also do is set MailWasher to use SpamCop, a global anti-spam organisation. Every email is checked against a database of known spam emails and can be automatically marked by the program as spam. If you get a spam email that has never been seen by MailWasher before, you can submit it so other people get it marked for them automatically.
You can do bulk deletes of spam with a single button and it saves a lot of time. There's other programs that do much the same thing.