Some of my grandson's classmates liked his shirt and asked him where he got it.  When he responded "thrift store" they were kind of making fun of him for it.  I've been thinking of responses for him.  Here's what I have so far.  I'm interested in what others have.  I'm sure you can top mine.  Granted, some of these remarks might not cut the mustard in 6th grade, but it was a fun exercise.

Environmental Conciousness:
Dude, save the environment!  Shopping at thrift stores conserves valuable resources!  Repurporse!

Rebellious:
Stick it to the man!  Don't support big business!  Fight the system!  (I must like excalamation points)

Social Justice
Most clothing is made in third world sweat shops.  We really need to stop supporting capitalistic suppression of the third world.  Support fair trade!

Frugal:
What kind of idiot pays $20 for a shirt I can buy for $2?

Pragmatic
Hey, it's not worn out, it's just broken in.
Yeah, we had better uses for our money than $30 bucks for a shirt I'll probably trash in a month anyway.

Pugnacious
Yeah, it's from the thrift store.  Want to make something of it?

Spiritual
My value doesn't depend on fancy clothes. 

Alt fashionista:
More variety at the thrift shops, rather than a single years fashions, you get to look at 20 years.  Great place to go for the retro look.

I like this style better and it's not available at Walmart.

Mick, great question and I like your responses.

For a kid, I think the best answer would be "My Granddad bought it for me. Isn't it neat!"

Kids can be really cruel and they are not interested in saving the world. 

I still like your responses!  And they would be great adult to adult.

"They treat new clothes to give them a worn look, but now you're looking at the real thing."

It's a great shirt!  It was probably some guys favorite shirt, and then he grew out of it.  I saved it's life.

Shhhh if the other people all start shopping at the thrift store, it'll cause the prices to go up. ;)
Just kidding. I feel like thrift stores are a good stepping stone towards cottage industry/industriousness/frugality and away from big box consumerism. You can always pull the "are you judging me based on my clothes, really??" routine but this only works on some people, probably the people who already shop at the thrift store anyway. You can also angle it as helping out whatever dubious charity is associated with the store. OR and this is the cool one, you can be REALLY good at shopping at thrift stores and everyone will think you paid $$$$$$$ for your super swag clothes, especially if you spiff them up a lil before wearing them out.
I like skirts but I HATE elastic so I went ape with a seamripper on this super awesome skirt, and voila! A drawstring later and not only do I look fabulous, but I'm also comfortable and I feel super industrious for not very much effort. I have a garment that is superior to anything I could afford off-the-rack. I regularly find stuff with the tags still on that were originally $90 or more and I pay maybe 3 bucks.

I had a friend, an engineer married to a dr. (with several kids) who confided to me that she only bought Nordstrom's brand because she liked the fit and the clothes, but she only bought them from thriftstores.  She had a regular schedule she followed and said it only took a few minutes per store, because she knew the store, knew where to look and had in mind what she was looking for.