Sometimes you have to stay on the desktop out of necessity. Can't intercept low-level keyboard events or manipulate the file system, for example, from the web.

Not a 'startup' per say but I'm in that boat. If I wrote this as a web app, it would work only on my website. As a desktop app it works in every open text-field, regardless of the program. http://onehandkeyboard.org

Also check out the the Business of Software forum, lots of desktop based app developers there. http://discuss.joelonsoftware.com/default.asp?biz