We in the web design business often talk about what users see above the fold. The assumption is that people may not be compelled enough to browse down. But there are certain situations where the most suitable “browse” direction is sideways and not down. TheHorizontalWay.com is a collection of sites that turn our preconceptions on their ears. Of particular note among the collection is Interview Magazine, which uses the orientation for both novelty and to avert long load times.
The only downside of this approach that I can think of — aside from being slightly disorienting — is the mobile edition of a site would be difficult to maintain, since mobile pages are more traditionally vertical.
Can you think of other potential programs with a horizontal design?