I am a HUGE fan of the Bad Behavior plugin:
Bad Behavior complements other link
spam solutions by acting as a
gatekeeper, preventing spammers from
ever delivering their junk, and in
many cases, from ever reading your
site in the first place. This keeps
your site’s load down, makes your site
logs cleaner, and can help prevent
denial of service conditions caused by
spammers.
We started using Bad Behavior on our tech blog and noticed an immediate reduction of spam, as shown below.
Here is our full article on Bad Behavior: http://www.techerator.com/2010/05/significantly-reduce-website-spam-with-bad-behavior/