Well, the main different is probably features. Plesk is good software, but I think both cPanel and DirectAdmin offer better choices. A good analogy for Plesk is the clunky Windows feel to it, and things are sometimes tucked away. From the administrator side, Plesk "takes over" the various services to a greater degree, and tends to be a bit buggy and complex to fix when an issue does arise.
As far as multiple websites, cPanel/WHM is much easier to use (IMHO) than Plesk, and this is one of cPanel's strengths. Plesk, as of a few months ago when I last used it, lacks a true reseller setup.
