On my site, the 300x250 , 336x280, medium & large rectangles are the most successful ad sizes.
It is a site, like many, which features articles. I normally use a classic 2 column layout for my pages, with the article presented in the left column and a right column for everything else.
After extensive testing in the past, the medium and large rectangles have always performed best when embedded in the content, aligned to the left.
I have a heading, a few lines of content and then a rectangle ad floated to the left, so text can be displayed to the right of it.
On a screen with a vertical resolution of at least 768px, the rectangle is still mostly above the fold. When viewed from a mobile, the ad is a scroll or two down.
I don't have a specific question about this position, more I would like to hear peoples thoughts on how they feel if this affects usability too much - it's a distraction from the article as the ad is in there right next to it, but that's the whole point.
I am thinking that whilst for me this is the most profitable area, perhaps in the long term it could be detrimental. Another site may be less likely to link to an article with an ad embedded in the content like this. Perhaps search engines may drop a point or two for ads in this position.
Many sites I visit with good articles have these large rectangle ad blocks positioned at the beginning or end of the article or on a side bar to the right. Perhaps this is due to limitations of their content management system.
Anyway I would be interested to hear peoples thoughts and reasoning on medium/large rectangle placement. I am currently redesigning my website and scrutinizing everything.