Without replicating too many of the above suggestions:
Reply All – Similar to This American Life
S-Town – A short true life series that comes across like a novel, brilliantly put together.
Revisionist History – Malcolm Gladwell’s project, bit like the best of Freakonomics.
The Butterfly Effect – Jon Ronson look at tech and porn. Not available ’till the Autumn but looks like it’ll be interesting
Longform – Specifically about journalism but can be interesting if you pick and choose a bit.
The Guilty Feminist – Mostly female perspective on social issues and feminism
Ear Hustle – Life inside San Quentin prison, produced by prisoners.
The Reith Lectures – Recordings going back to the 1940’s
More general chat show format podcasts, how informative they are depends a lot on the guests
Marc Maron’s WTF podcast
An Irishman Abroad
Heres The Thing with Alec Baldwin
The Comedians Comedian – Discusses the process of comedy, normally more interesting than funny.
The Adam Buxton Podcast
More light hearted ones.
Richard herring Leicester Square Theatre Podcast – Interviews but generally more comic than informative
Beef and Dairy Network – Surreal comedy based on the beef industry (but nothing to do with it really)
The Bugle – Andy Zaltzman topical news podcast
If I had to recommend just one podcast it would be S-Town.