From a user POV it's less the position of the ads and more the site design IMO. There are some sites that look great, even with aggressive ads. Others have ads in the same spots but look spammy. Finding that balance is tough, but there are lots of examples to pull inspiration from.
As for page layout, my meager understanding is that it's something like a content:ad ratio within a specific viewport.. So ads ATF won't necessarily hurt, but you need some other good stuff mixed in to sustain a nice balance. I could show you some examples of thriving sites (not mine) with side by side 300x250s at the top of every page. They have tons of other solid quality signals as well, though, so it's not cut and dry. Is it ever?