On the forum I run, I have all new members "moderated" for their first post. I then manually approve each first post that a member makes. (I actually have several members authorized to approve posts.) If it is spam I just delete the user. It only takes a few minutes a week. There is a "member upgrade" script that runs hourly and if a new member has one or more approved posts they get upgraded to non-moderated status.

I also have a simple question-answer challenge and a captcha.

All of this took a few hours to set up but it has paid off in the long run. My forum uses vBulletin so I don't know if these options are available here.

Since I implemented this process not even one spam has slipped through to where the general readership would see it.

My profile shows my forum address. If you try to register you will see this method in action. The forum covers a pretty obscure topic so I doubt anyone will want to actually join, though!

Edit: I also have a tool to scan the web logs and block abusive IP addresses. This helps a lot!