I'm a member of the Compact (a non-consumer, buy only used -- with a few exceptions -- movement), so I love me some thrifting. A few pro-tips:
1) Shop thrift stores in upscale areas if you are looking for designer or work clothes.
2) Get friendly with the staff and learn which tags are half off on which days.
3) See if there is a Goodwill Boutique in your area. These small Goodwills are where the better quality items and items with the tags still on often end up.
4) Don't forget consignment stores, especially for women's work clothes. A bit pricier than a thrift store, but killer deals none the less.
5) Cruise Craigslist for garage sales. Once again this is especially helpful with women's clothes, but I see men's stuff quite often too. We have tons of garage sales where new stay-at-home-moms are unloading there former corporate garb, and they advertise them as such.
6) Check items over carefully. Small imperfections, like a popped button, you can repair. A totally blown out zipper? Not so much. And if you do find an imperfection, ask for a discount! It's expected and usually given.
7) Patience, Padawan! You'll never find it all in one visit.
Other than underwear and a few electronics, pretty much everything we own is second hand. You wouldn't know it by looking at us or walking through our house, though!