Doug Kaye is one guy who REALLY knows Audio (He is the man behind IT conversations). At the very first Portable Media Expo I attended a seminar on better audio quality, and it was one of the most informative seminars I attended.

Doug and Paul Figgiani go over many examples of Skype vs hybrids.

You can hear the different examples side by side. Here are some other tips they recommend.

Use a USB headset.
Close any programs that are running in the background (like iTunes, IM,).
Have a good connection (100kbps) to be safe

About the 6 minute mark he really gets into some other great tips. Very informative.

Check it out at