Most of mine are videogame related:
1Up Yours & Games for Windows podcasts are ABSOLUTE MUSTS, as is the video cast 1Up Show. It sounds sad, but I legitimately look forward to those podcasts.
Gamespots the Hotspot
Downloadable Content: Penny Arcade podcast
What's New Now
Buzz out Loud
And then vidcasts like Diggnation, DL.TV, Cranky Geeks