I have stopped using any plugins and have enlisted the aid of the WP 1.5beta comment blacklist. It works. I have listed in there common spam words, the munged “names” of the spam posters, entire URLs which are commonly found in my spam, and the two IP addresses that some bright soul figured out were probably responsible for most of the spam about at the moment. Its not a definitive list by any means, it’s a list which applies to the spammer who has been hitting my site through a series of zombies and ostensibly terminated accounts..
However, for the first time in three weeks I have comment moderation switched off, and I feel like its *the* solution for the moment.