I second Scott Sigler, good hardcore pop-sci-fi fun.*
*Okay, I’m kind of biased, he’s one of my really good friends… I’ve produced much cover art and other stuff for him.
The Canadian Broadcasting Corporation (CBC) has a bunch of cool ones:
Ideas - Highbrow discussion of random stuff
**Definitely not the opera **- CBC has (at least) two radio networks, one of which plays opera on the weekends. The other… does not. Fun pop culture stuff
Quirks and Quarks - Weekly general science show.
Vinyl Cafe - Folksy story-telling about small town travails. Similar to that Lake Wobegon guy. Can get a little precious, but can also be very funny.
White Coat, Black Art - A doctor does a weekly series about health care issues. Really, really interesting, especially as my wife is a nurse.
Other stuff:
You Look Nice Today - The funniest podcast I’ve ever heard. A little erratic when new ones come on.
The Business - The business side of Hollywood.
**Filmspotting **- The best film podcast I’ve ever heard. Wide-ranging, lots of recurring segments, funny and insightful.
Creative Screenwriting - Wide-ranging interviews with screenwriters. Like ‘Inside the Actor’s Studio’, but with writers.
This American Life - The best podcast in the world. Funny, moving, insightful, brilliant stories of everyday Americans, extraordinarily told.
Some of these have been mentioned but I’ll just list the ones that I enjoy listening to regularly:
Doug Benson’s “I Love Movies” - Benson hosts a show at the UCB Theater in LA where he has two or three guests on to talk about movies and play various film-based games with him. The guests are usually other comedians (Paul F. Tompkins, Chris Hardwick) but he also gets actors once in awhile (Jon Hamm has been on once or twice). It’s always good for some laughs.
Comedy Death Ray Radio - Hosted by Scott Aukerman, he always has two or three guests on talking about all sorts of topics. Usually the guests will come on as some sort of character they’re working on (Paul F. Tompkins did an entire show as Ice-T. Thomas Lennon co-hosted the show once as some character named Little Gary that just cracked my shit up.) Interspersed with the talk he plays various comedy songs… everything from Flight of the Conchords and Lonley Planet to Weird Al and Joe Piscapo.
**Smodcast **- Kevin Smith and (usually) Scott Mosier talking about anything and everything. I was at Smith’s recent Q&A here in Chicago and he mentioned that Smodcast is his favorite creative outlet at the moment.
**The Dave Ramsey Show **- Just an hour of Ramsey’s radio show giving financia advice. I get a lot of good info from it.
**Stuff You Should Know **- Two guys from HowStuffWorks.com discussing a different topic each week. I find it pretty entertaining but I know others are put off by the hosts.
**Stuff You Missed in History Class **- Also by HowStuffWorks.com but hosted by two women. The show used to be better with their original co-host (a young kind of nerdy girl) but she left the company and was replaced with someone I don’t like as well. They come off as two sorority girls talking about history, but there is some really good info in them. I learn a lot.
Reasonable Doubts
Skeptics Guide to the Universe
Point of Inquiry
Skepticality
Savage Love
I Want your Sex
Pritzker Military Library
Slice of Sci Fi
The Bible Geek
Atheist Experience
The Non Prophets
Astronomy Cast