My favorite comedy podcast is Judge John Hodgman: http://www.maximumfun.org/shows/judge-john-hodgman and I similarly recommend anything else from the Maximum Fun Network: http://www.maximumfun.org/
Two other great podcasts, for those interested in US politics, are The Political Scene (from the New Yorker, http://www.newyorker.com/online/blogs/newsdesk/podcasts/), and Ken Rudin's "Political Junkie," done by a funny former NPR reporter and analyist (http://kenrudinpolitics.com/).
My favorite comedy podcast is Judge John Hodgman: http://www.maximumfun.org/shows/judge-john-hodgman and I similarly recommend anything else from the Maximum Fun Network: http://www.maximumfun.org/