Make an AJAX query for a cryptographic nonce to the server. The server sends back a JSON response containing the nonce, and also sets a cookie containing the nonce value. Calculate the SHA1 hash of the nonce in JavaScript, copy the value into a hidden field. When the user POSTs the form, they now send the cookie back with the nonce value. Calculate the SHA1 hash of the nonce from the cookie, compare to the value in the hidden field, and verify that you generated that nonce in the last 15 minutes (memcached is good for this). If all those checks pass, post the comment.
This technique requires that the spammer sits down and figures out what's going on, and once they do, they still have to fire off multiple requests and maintain cookie state to get a comment through. Plus they only ever see the Set-Cookie
header if they parse and execute the JavaScript in the first place and make the AJAX request. This is far, far more work than most spammers are willing to go through, especially since the work only applies to a single site. The biggest downside is that anyone with JavaScript off or cookies disabled gets marked as potential spam. Which means that moderation queues are still a good idea.
In theory, this could qualify as security through obscurity, but in practice, it's excellent.
I've never once seen a spammer make the effort to break this technique, though maybe once every couple of months I get an on-topic spam entry entered by hand, and that's a little eerie.