Conan was interviewed in the New York Times about his shift to the Tonight show. The following quote is about entertainment, but I think it applies to any creative endeavor, or possibly, any human interaction:

“In entertainment, you have to stake out what you think is right, you have to put out that signal, make sure it’s pure and then do it and do it and do it and know that they will come. And if they don’t, you have to pack up your bags and say: ‘I enjoyed my time here. Sorry it didn’t work out.’ But the biggest mistake would be to alter my signal to make sure that I reach all these different people. Because then you’re lost.”

Agreed. This is why I always bristle when I hear people who are making some product for a “target audience” that’s not them. I’m not saying it’s impossible, but to me it’s hard to be genuine, and if you’re off by a millimeter, as Conan says, “then you’re lost”.