Nerd poker used to be the podcast I most looked forward to each week. Sark is the $h!+, but without him, Gerry and Sarah it just doesn't hold my interest anymore. I haven't listened to the last 10 or so. As long as I keep seeing "more red giants", "some more blue giants", "some more giants" in the episode descriptions, I think I'm done.
That being said, my new most anticipated roleplaying podcast is the Campaign podcast. It's a Star Wars based game and it's great. They are up to about episode 22. There is also a 3 episode prequel on the One Shot channel as well as a 2 episode pre-prequel that take place 5 years earlier. In addition there are 3 flashback episodes after episode 17 on the Campaign podcast, they take place roughly 15-20 years before the main story. You could easily start at any of those 4 and things would make sense. I'd probably recommend starting at the first campaign episode to see if it's to your liking.
If your a hardcore D&Der, Critical Hit might be for you. Great story and spot on with the rules and game mechanics. They recently started something new (modern city) that I'm really not in to, but the original campaign is hundreds of episodes long and worth a listen.
The Adventure zone has been mentioned a few times, I can definately endorse that.
Drunks and Dragons is OK, I haven't gotten very far yet. The same people make it as Cast of Thrones a Game of Thrones podcast.
Based on recommendations here I'm giving D&D with StS a shot. I've only listened to the first episode and I can't say I'm sold, but I will give it a few more episodes. Does anyone know if it's just the 2 players for the entire run?