One of the best performing sites I have in terms of CTR is very unattractive. It has a large garish image and 2 square ads within an article of text. Personally I think the ugly design contributes to people clicking through vs. staying on the page. I do not want to motivate people into making hideous adsense sites, just sharing a method that has worked very well, my average is 33% CTR on that site.
My suggestions are let the mouse follow the text on the way down the page and then have the ads inline with the mouse. The only way to seriously compete with adsense is to jump through Google's hoops. Write tons of content in a given niche, rank well, get organic traffic, and then capitalize by designing a template that works. This all takes a lot of trial and error but once you've found something that works, you'll enjoy the results.
Pm if you have any further questions.