A few days ago, my wife noticed that her iPod touch (2nd Gen) was draining battery like nobody's business! She would fully charge it, then within an hour or so, it would be dead or nearly dead. She is running 4.2.1 and it is well-known that the 4.x iOS has major issues with various generations of iPods, especially battery issues.
Of course, "Airplane Mode" solves the problem. It also defeats the purpose of having a wi-fi enabled handheld device. I did some poking around and stumbled across a suggestion to reset the network settings. At this point, I figured it couldn't hurt. So far, so good!
To reset your network settings, go to SETTINGS > GENERAL > RESET > RESET NETWORK SETTINGS
This will, of course, make your device forget everything it saved for your networking, so you will have to re-join your wireless network(s). But, already we've seen a MAJOR difference in her battery life. Evidently, the update process hoses the network connection such that the wi-fi never sleeps or runs at max or whatever.
People jumping from full factory reset directly to 4.2.1 say they have no issues. That leads one to believe that the issue is in the updating process. Well, whatever the problem, the fix at this point seems to be to reset the network settings on the device.
Hope this helps someone else!