Two things, both on a large Wordpress installation:
While testing a migration of some custom tables, I deleted all our custom tables to do a clean run of those migrations. Unfortunately, I was in the SequelPro tab of the production database, not my local database.
I thought we were caching stuff in memcached, but the way you get Wordpress to use the cache is really hacky and I couldn't get it to work locally. So my typical workflow was to comment that file out, at which point Wordpress will start caching stuff to the database instead. Well, I accidentally pushed that commented file into production, so this large site with thousands of concurrent users started caching everything to the database instead of memcached. It didn't take long for MySQL queries to get exponentially longer due to millions of rows being queried on each request, bringing the entire site down.
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Two things, both on a large Wordpress installation: