I have had a big problem with Mailman yesterday and today: two or three hours after I sent out my "big list" message (150 000 subscribers), Mailman started to spend all its time using CPU, for ages. In fact, it was the bounce runner that had started to send out the "probe" messages, one by one, making VirginRunner lock the list repeatedly, and holding the lock for 15s each time. Meanwhile the web admin interface was unreachable (for that list), and other scripts waited and failed.
You may want to disable VERP_PROBES by update your mailman to the latest CVS. It was introduced in 2.1.5 but made optional for backward compatibility. I remember you have updated around 16 Oct but CVS commit was done 22 for this fix. (Remember you need specify Release_2_1-maint)