From billhiggins.us:

If you’re considering or actively building Ajax/RIA applications, you should consider the Uncanny Valley of user interface design and recognize that when you build a “desktop in the web browser”-style application, you’re violating users’ unwritten expectations of how a web application should look and behave. This choice may have significant negative impact on learnability, pleasantness of use, and adoption. The fact that you can create web applications that resemble desktop applications does not imply that you should; it only means that you have one more option and subsequent set of trade-offs to consider when making design decisions.

See also: The Other Road Ahead by Paul Graham. Scroll down to the section entitled ‘Just Good Enough’.