I had a kernel panic today (quad-core iMac running Mac OS X 10.6.8), and when my Mac started up again, the Command and Option keys on my keyboard (a Microsoft Ergonomic Keyboard 4000) were reversed. Normally, this wouldn't be a big deal—one just goes to the Keyboard Preference Pane and changes the modifier key settings to swap the two keys. But in this case, no amount of changing the modifier key settings had any effect. This is incredibly frustrating for someone who is nearly 100% keyboard shortcut dependent.
After over half an hour of trying various things like rebooting, resetting PRAM, trashing assorted .plist and preference files, I finally unplugged the Logitech wireless transmitter that talks to my Logitech Performance MX mouse and set modifier key behavior using an Apple Magic Mouse. It worked, and the settings stuck even after I plugged in the Logitech Unifying Device (the USB transceiver). Strangely, if I go to the modifiers preference now, it shows that it has reverted to default, even though my keyboard suggests otherwise.
If you've discovered this site because you have same problem, unplug your Logitech mouse and make the changes again using an Apple mouse. I hope it works for you!