I would take a look at the Arduino microcontroller board - you can wire all sorts of things into that (buttons, sensors) and interface with it using the .NET Ports classes.
Might be worth a look at Phidgets:
http://www.phidgets.com/index.php
They do many little USB I/O devices, and the code samples are there on the site too.
I'm looking for the same thing. this might do the trick:
Haven't tried it yet, but he has code to run a shell command or simulate a keypress and the source code is available if you need something different.
And for Linux: search freshmeat dot net for usb-panic-button-daemon project. (I'm a new user, and can't post more than one hyperlink!)
And another thing I just found is that Griffin makes an SDK available (at least they used to, I'm waiting for a reply) for their PowerMate knob to get it to simulate more than mostly just keypresses.
BTW I'm looking for USB buttons, but I could use serial too, come to think of it.