I've had the same sort of issue yesterday with 1.2.2, all of a sudden 404's but with a additional 'No input file specified' coming from the php backend(and 1 sec later from nginx cache 'HIT'), one minute later and everything was normal again. No floods, normal traffic, no additional log entries... Only backend effected, normal static sites worked ok.
Restarts did not help either which is the weirdest, but then again I did change alot recently like using nginx caching with the php backend, php code RC cacher. And I did wanted to update php anyway to the 5.4 branch, so now updated everything to 5.4, changed a dozen php apps to work properly with 5.4 and now waiting to see if the issue happens again.
There are memory corruption issues with php 5.3 which have been fixed in svn but not compiled/released yet, 5.4 does not have these issues so hopefully 5.4 solves this weirdness.
It does sound like a php issue (75% sure) but it could be a nginx issue as well like for some reason not passing data to the backend, however it is extremely weird when restarting nginx and the backends the problem persisted ! either wait without restarting or restart 3-4 times before things are back to normal.