[CPops]

The right choice depends on your target market and what your overall goals are.

But my opinion is that for startups, the smartest way to utilize limited resources is to avoid supporting things like IE6 and users without JS enabled and just build your applications for early adopters, because thats who is going to use it initially anyway and make or break your business.

The answer might be different if you're part of an established company with dozens of programmers and you have the resources to support everybody without any problems.