Currently we use jQuery to add RIA goodness to our apps, but recently we have been implementing the Coveo Search engine into our Sharepoint portal and found that ScriptSharp
At my last company I used Script# very extensively. I managed to write some cool controls (in fact an entire client side MVC stack) which I couldnt have done with my knowledge of javascript. However, I wouldn't use it again for several reasons
The tooling for js is only getting better and until Script# is open sourced, it's at a standstill.
If you're interested in cross compiling, you could also take a look at the http://jsc.sourceforge.net/ project, which lets you use .net 3.5 and compile to JS, Java, Flash or even PHP! Not sure how efficient the code that gets produced is though...
edit: there is a new project called JSIL which also rewrites .net code to JS