I've never tried this, but I wonder if it would be possible to make it so that people don't have an option to edit their signatures until they have a certain number of posts. You may be able to make it by making a group that can edit signatures and setting it so that normal registered users can't. Then you can set up an automatic promotion to the "sigedit" group when they meet some criteria. Chances are, spammers wouldn't know why they can't edit their signatures any more. They'd likely just give up.
Spam has been bad recently for us, too. I've enabled manual registration approval. There are two groups of spammers coming after us that have been able to get past honey pots in our registration screen (presumably because they are human). It's super easy to determine which of them are spammers based on the location derived from their IP number, so I just block them before they even join.