I originally required registration to comment to cut down on spam, before Akismet was easy to use. It was a crappy requirement, who wants to register with a random blog just to leave a comment? So I turned it off, and the only purpose it’s served since then is to provide a useless vector for spammers.
Since I wasn’t using that data for a honeypot or anything, I’m just turning it off and removing all the accounts, even the few legitimate ones. They’re just not needed anymore.
I’ll be relying on Akismet for now; if that doesn’t work, in the future I’ll require an OpenID.
I use a combination of Akismet, Intense Debate and Open ID on my blog. That combination reduced the time required to handle spam to 5 minutes a month.
http://www.intensedebate.com/