I've found the best solution is to use a variety of strategies. We recently switched a forum from PhpBB to MyBB in the hopes that a slightly less popular platform would get less spam... we had a spam user sign up and post within 60 seconds of finishing our conversion.

However, we set up a StopForumSpam plug-in, a time-based plug-in (if you complete the registration page in < X seconds, you're probably a bot), and a custom questions plug-in, and we haven't seen any spam since. If they start figuring out to break through those walls, we'll try a few more... (On the other hand, it' s a small enough forum that I don't know if we're missing false positives.)

Yes, it's a cat and mouse game, but it's one you can generally stay on top of with minimal configuration once you understand what the spammers want and how to use your platform. And I have to admit there's some thrill involved at successfully thwarting their plans...