Gawker Media, publishers of Lifehacker amongst other things, have a great idea for their unsold ad space: they put art work in it. Traditionally this space is used for in-site promotion (the latest features, mailing list sign-up etc.), cross-site promotion (sister sites) or free ad space as sweeteners for clients. The genius of putting art work in the gaps is that it makes the sites look really cool, while raising consumer interest in those spaces on the page, thereby raising the value of the ad space that is sold. I would be really interested to know if it’s helped their click thru.
You can read more about their policy on Gawker Media’s website.