MySpace uses ASP.NET ( source ). Lots of great sites. However, I would ignore the Many Fish example. From my recollection of the stories I read about, they just use the HttpHandlers for output, generally skipping Webforms stuff. You could probably get Webforms to scale, at least you absolutely need to. The most popular frameworks can handle high load, it depends only on the code and who writes it. Anyone can program the site in any framework that will not scale, but not vice versa.
As for scaling, the most important thing is caching, caching, caching. All large caching sites are widespread. Facebook has thousands of caching-only servers. This is only the beginning, but.
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