I agree with the points Joel makes on using different languages. I have talked about this in the context of language-centric software development. The real power of languages comes from their economy of expression when they are used in their native problem domain. For example, look at string processing in Perl and C#. The example will be to find and replace 'abc' with 'def' in a string. This is Perl's home territory and so it has a very succinct syntax:
s =~ s/abc/def/g;
string s = Regex.Replace(s, "abc", "def");
This isn't to detract from the nice design of C#, the CLR and the FCL. I am really enjoying learning C# and I am finding the class libraries are consistent and easy to navigate. With my limited understanding of the CLR I do not see that .NET restricts the design of the language so much that they will all look like shadows of C#. For example it should be possible to create a Perl.NET that has the syntax of the Perl code above but that compiles into the same MSIL as the C# code. I look forward to seeing other languages ported to the .NET framework.