This is a business decision rather than a design decision.
There is a cost to providing a version of the website that works without JavaScript (or Flash, or Silverlight). The business has to decide whether the loss in revenue/visitors is worth it or not.
So if it costs $10,000 to do write this version (the number might be on the large side, but it's there for this example only) then will the business recoup that outlay over the lifetime of the site? If not, then don't provide that version.
However, if it only costs $100 to write this version then it would make sense to provide the graceful degradation.
Having taken the business decision to only target JavaScript enabled browsers and expect that your users will have JavaScript enabled then it makes perfect sense to make your application take advantage of those features you now have available. The only thing you will need to do is (like Stack Overflow itself does) is put up a warning that the site won't function correctly if the user hasn't got it enabled.