Design Elements that can Affect Your SEO?

Jo – what do you think of the SEO strategy using different colors and font sizes in a post? Personally, I think it distracts the reader and changes the focus away from the content. What do others think?

I am not a fan of those strategies either, for two reasons. First of all, as you mentioned, they often times go against the interests of your readers. Using colors and different font sizes just to communicate to search engines that those words or sentences are “special” would affect negatively the visual appeal of your content.
If you do this naturally and with user experience purposes in mind, then I would say it is OK. Using colored post titles and sub-headers, for example, is both SEO sound and useful for the readers.
The second reason is related to the real effectiveness of those techniques. Although I agree that search engines certainly analyze many design and layout elements on a web page, I don’t think that they put too much emphasis on font colors and sizes.
The usage of the bold and the italics typefaces are also interpreted by search engines, although lately I suspect that they are losing value too, because people always try to manipulate those (i.e. by making their main keywords on any given post bold).
I believe that more important than those are the meta elements. That is, the tags and attributes that go behind the scenes on a web page (i.e. inside the HTML code).
The H1, H2, H3 tags, for example, are taken into consideration by search engines to determine the structure of your content, and to filter the most important sections out. Your single post page titles should therefore always be wrapped by H1 tags (as opposed to using the H1 titles on your blog name or logo, as many people do).
Finally, it is also important to make sure that your main content comes as soon as possible on your code. That is, if you have a sidebar and a main content area, structure your design in a way that the main content area loads first, and after that the sidebar, footer and so on.
You can take a look on the code of Daily Blog Tips for example. Right after the navigation bar the main content column loads, and after that the left and then the right sidebars.