High profile advertisers, instead of trying to shoehorn into intrusive slots between the site itself and the content you're trying to consume, would be better advised to think even bigger.
Many sites can be given a complete visual alteration simply by assigning a different template - for example,
many sites based on a modern CMS will allow the template to be switched with relative ease. The template simply supplies the presentation layer - the positioning, the size, the typography, the graphical furniture, the colour, the space, the feel, etc.
Top-end advertisers could be offered the most premium spot on a high-traffic site, for a day. The opportunity to provide their own exquisitely designed lush seductive and hopefully agreeable template, in place of the site's own normal template. This template, to derive best effect, would in fact be a one-off, never used again.
The advertiser's template would of course have to be a viable co-branding, otherwise people will think they're not where they thought they were, and lose trust, but this is a simple matter for an ad agency to encompass. I myself have created many excellently-accepted co-branding design projects in the past - it's a fine balance to achieve but not impossible if you're good at it.