Just a note on sites with a lot of members - I'm sure more than a few of them have a lot of really active genuine members, but in my experience - I run a vB forum which has been operating for nearly 9 years and is very location specific (ie the forum is very specific to Australia).
Because of the popularity of the forums and the good search engine rankings we get, we've always been a target for spam. When trying to deal with this, I decided to try tracking the geo-location of IP addresses of registering members (using the Maxmind database). I was astounded to see so many people registering from countries outside of Australia (in particular China, India, Philippines, Malaysia, etc). I also ask people for their location when registering (mandatory user profile field), and discovered that almost all of these users were lying about their location. Further analysis of existing users showed that they were also the people posting all the spam.
So now, I have an automated system to check all new registrations and anyone from a country on my "blacklist" gets placed into moderation so I can decide quickly whether to allow them in or just delete them. This has already made major progress with spam.
The thing that surprised me was just how many of these registrations we were getting each day - we get 10-15 new registrations a day, and nearly half of them are from people outside of Australia - almost all of whom lie about their location when they register.
Looking back at the users in the database, we have a LOT of members who were not legitimate users and only signed up to spam the forums.
Naturally, this approach does not work quite as well with a more international forum - one of my other sites is almost as busy and has a very international focus, with quite a few legitimate members from those regions where spammers tend to come from. As such, I've needed to take a slightly different approach and don't auto-moderate such users. Fortunately, spam is less of a problem on that site - possibly due to the nature of the content.