either make the ad in complete contrast to your content, OR make it so similar to your content that users dont' know which one is ad and which one is content.
Make your content more comprehensive, the ads which are displayed will most likely suit to the visitor. And the more relevant the ad, the more likely the user may click on the ad link to find other information.
3 ads is the maximum that you can show. Try to use ad rotate to reduce ad blindness of your visitors.
Its when your visitors noticed your ads and starts ignoring those location because they already know that those spots are ads.
Best is to be very related to paid competitive niches, My average CTR is %20 - %30 means targeted visitors. No need many ads, sometime less ads earns much more.
Try Adsense experiment which allows you to change the color of your ads and opt the one which gives you more CTR. Change the placement and check the CTR, a leader board just below the top menu will get you better CTR