E-Mail coming from an obvious spam domain? Add them to /etc/mail/access. After all why even waste the bandwidth accepting spam in the first place.
This is pretty much my approach. On my RaQ 4r, I use the DNSBLs to stop the majority of spamious connections.
Then I periodically (every 1-3 days, maybe more) check my maillog for stuff that got through and add the domain to /etc/mail/access... actually I generally set up an ipchains rule, either for the single IP or a network block... I figure that if I get spam from an IP, I might get some other nastiness from it as well as some point, so I just cut them off at the knees ahead of time. :)
An added bonus of the ipchains blocking is that I set up a Perl script to sweep through /var/log/kernel looking for the :1433 and :445 blocks (various MS-related worms), and automagically add the IPs to my ipchains drop list (again assuming that if they are still infected with Blaster, etc., they might at some point be turned into SMTP servers, etc., attempting to connect to me, so I cut them off ahead of time).
I also throw in rules via procmail for the latest round of viruses as they occur to help block anything that might slip through. And of course some procmail "white list" rules to let some stuff straight into the inbox...
I now end up receiving maybe 1-5 spams per day across about a dozen email addresses on 4 different domains I have on my RaQ.
The DNSBLs, though, especially Spamhaus, are doing the heavy lifting for blocking spam for me...