A friend at a very-high traffic, major brand-name site asked me for some suggestions for selling off excess ad inventory. They have a stable of existing major advertisers, but still have inventory available. Good ad control (i.e., preapproval) is essential to avoid conflicts with existing advertisers and company image, which makes Adsense (my first thought) unattractive.
Burstmedia came to mind, as did the possibility of targeted affiliate ads... any other suggestions?