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If all you test is the layout then, for the most part, you are Right! Right! Right!

But...

Even with little traffic, you can still achieve significant gains by focusing on the copy as opposed to the layout and colours.

I learnt this mostly with Adwords. At the prices they charge now, you just have to find the gains wherever they are.

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Same principle applies to copy, especially to microcopy. If you change a couple of words in a headline, it rarely makes a difference.

Depends where the copy is. Changing a couple of words in an email subject line can and often does make a huge difference. Of course the fine line you walk is that some of the most effective words at driving behavior (Free! Now!) are also effective at getting you marked as spam.

I think wording in the subject line is important, because it is the only thing a user sees. There are no other factors that affect whether he will open it or not.

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