I'm using Intego's Personal Anti-Spam X4 software, it works with Apple's Mail and MS Entourage only. It's good at separating out spam from good email, but first you must mark which ones are spam, and then it learns as you go. However it downloads all email using multiple filters (blacklists, URLs, attachment types, whitelists, lexical filters). Unfortunately it doesn't block the downloading of spam messages.
If you want, there is a special pack version called "Internet Security Barrier X4 Antispam Edition", which has Virus Barrier and NetBarrier (firewall) programs along with the Antispam app.
On a personal note, I combat spammers tendency of putting random letters at the beginning of email addresses by just keeping the last part of the email address from the @ symbol onwards (in my blacklist), and telling the program to look for addresses -containing- this part of the address.
See:
http://www.intego.com/personalAntispam/