Happened to me a couple of times last thursday - I opened the sets and all I got back was a thumbs up from one of the girls and no verbal response.

They did this in a sarcastic way implying that they're not interested in talking to me. I tried to follow up by calling them out on their reaction to my opener but I just got the same response again.

What should I have done?

You haven't said anything about where this happened. Also we don't know what your body language or tone of voice was like. If you give more detail then people might be able to tell you how to "do it better." Otherwise, what you should do is read the forums a lot and especially concentrate on the non-verbal parts of the pickup.

There is always the possibility that you ran into some real bitch that you should just forget about. I think that happens a lot with very young women, who don't really know themselves, and thus don't know how they feel about all the men who are constantly hitting on them.

They were both in different bars.
My body language is generally very good and I open indirect without showing too much interest.
I try and give off the vibe that I'm just a social guy who like to talk to new people.

you might have been too direct, which leads any group to close up, and go nope get out. If you're out during the day, its tough to just go up to a group, because they're busy, for me, it has to be totally indirect, as if you're just making small talk, or you have a thing you need to do. If its at night, all girls are on the defensive because they're expecting people to come up to them.

What did you actually say as you're opener? i find its gotta be less direct that how're you guys doing? or are you having a good time today/night?, but also more interesting than weather's nice today?

Its the lamest thing to get a sarcastic 'fuck off' response, my only advice to avoid this, is to go in even more indirect. I find the more random your opener, the more indirect, and the less threatening/chat up line-like it is. I opened a girl with her headphones in with 'do you know anything about artificial intelligence' and we started talking about robots, and minds etc. it was great.