Thank you very much gummybear and c0d3h4x0r! I had been having the exact same problem gummybear described for a while now and spent countless hours trying to determine the source. I knew it wasn't specifically a problem with Win7 x64, because Nestopia had been working great for me. I noticed the problem after installing a new video card a while back, going from an nVidia to an ATI one. So I was under the misguided belief that it was a video driver issue and the sound glitching was some side effect of it being unable to sync correctly.
When I think back, I do believe I updated Creative drivers sometime around exchanging video cards. I guess I'm not surprised it's a problem with their drivers, they are notoriously shitty. Only reason I still use their cards is because all others seem to have problems with multichannel sound in games.
Anyways, what I've done is left my Creative X-Fi as the default system device and reinstalled my HT Omega Claro+ (C-Media based) and have Nestopia use that card. Then I hooked up the line out of the Claro to the line in of the X-Fi so I get the best of both worlds.
BTW, how did you determine it was a sound driver issue? How is Nestopia using it in such a way that causes problems but no other emulators (or anything else) have this problem?