The Nerdist Podcast
The Nerdist podcast is hosted by Chris Hardwick. He basically sits down and talks random stuff with his friends. There are guests and the topic is usually a science or geek themed topic of some kind. The podcast is very professionally done with great sound quality. Recent guests include Seth Rogen and Dana Carvey. Each episode is different so it doesn't get old after a few weeks.
If you're looking for a geeky podcast, The Nerdist is for you!