dwanthny has some very good advice. Follow it.
The two biggest problems I've found are a) USB 1.1 ports, and b) unpowered USB hubs.
USB 1.1 is flaky as standards go, and depending on the PC involved, if it has 1.1, it's possible that it just plain doesn't like your Reader, and is having a snit. The Reader sucks down power -- if it's on an unpowered hub, it can in fact discharge. So if you're not going direct to the PC, use a powered hub.
System rebuilds rarely solve this sort of problem, and they're a nightmare. I use XP myself, and it's never been unhappy with my Reader -- although some ports on one of my comps are (specifically, the front-panel USB 1.1 ports). So test with a known good device before you think about doing anything drastic.