Paper Prototypes Over Computer-Based Tools

When it comes to prototyping Web site design, paper prototypes tend to have an advantage.  In the book, The Design of Sites, by Douglas K. Van Duyne, James A. Landay, Jason I. Hong, the authors explain some of the advantages.

Iterate and Explore the Design with Paper Prototypes
Van Duyne, Landay, and Hong write:

"Research shows that designers who work out conceptual ideas on paper tend to iterate more and explore the design space more broadly whereas designers using computer-based tools tend to take only one idea and work it out in detail."

Low-Fidelity Prototypes Over High-Fidelity Prototypes
Van Duyne, Landay, and Hong write:

“Nearly every one of the designers we have talked to has observed that the discussions is qualitatively different when people are presented with a high-fidelity prototype. Clients often respond with comments like, 'I do not like your color scheme,' or 'These two buttons need to be aligned correctly.' When presented with a low-fidelity prototype, however, clients are more like to say something like, 'These labels on the navigation bar do not make sense to me,' or 'You're missing a link to the shopping care here on this page.' In other words, with low-fidelity prototypes, which lack irrelevant details like color, font, and alignment to distract the eye, people focus on the interaction and on the overall site structure. “

However, it's worth noting that software that emulates paper prototyping can be very helpful.  One example is Balsamic Mockups.