On the web development side ASP.Net is really hard compared to other frameworks out there. Until ASP.Net MVC, there wasn't a quick and easy method to implement URL rewriting for example. On the ORM side they seem to be changing their mind every year they ditched Linq to SQL in favor Entity Framework which really doesn't work as seamlessly as they make it out to be. Add to this the fact the startup has to buy licenses for the server, the costs add up as you scale up. I know there is Mono but there it isn't easy to port everything to it, the implementation isn't exactly complete.
.Net has its place for example if you are writing a Windows only desktop application .Net is by far the easiest framework MS had to support it. I believe Xobini uses .Net. Again writing cross platform desktop applications doesn't look as appealing to me. Silverlight 3 is almost here but it still yet to get font rendering and printing right.