One layout that worked well for the majority is the Large Rectangle (336X280). Why choose this format out of the many you can use? On the whole because the ads will look like regular web links, and people, being used to clicking on them, click these types of links.

Construct a custom palette for your ads. Choose a colour that will go well with the background of your site. If your site has a white background, attempt to use white as the colour of your ad border and background. The idea to patterning the colours is to make the Adsense look like it is part of the web pages. This will result to more clicks from people visiting your site.

Get rid of the Adsense from the bottom pages of your site and put them at the top. Don't try to hide your Adsense. Put them in the place where people can see them fast. Preserve links to relevant websites. If you think some sites are better off than the others, put your ads there and try maintaining and managing them. If there is already lots of Adsense put into that certain site, put yours on top of all of them. That way visitor will see your ads first upon browsing into that site.

There are many other Adsense sharing the same topic as you. It's best to think of making a good ad that will be a bit different and distinctive than the ones already done. Every clickthrough that visitors make is a point for you so make every click count by making your Adsense something that people will click on.