Each vehicle series has its good and bad points. You just need to pick an era or type and see what you can find out.
There are some universal things to look for though.
1. Servicing records. If the oil and fluids were changed regularly, that means less wear and tear on the engine.
2. Few, if any, modifications or alterations, unless made by someone you actually trust. That applies especially towards lift kits and engine swaps.
3. RUST! The less rust, the better.
4. Interior cleanliness. This includes the engine bay as well as the cab and cargo areas. Food stains, cigarette burns, oil and coolant covered engines and dented to hell pickup beds are all signs to look out for. This shouldn't kill a deal, but they should be asked about.
5. If you're not sure, ask an expert. If you have a mechanical friend who works on vehicles of that type and era, he, or she, should be able to tell you more specifically what to look for.
6. If possible, test drive it. You can decide how you like the way it feels. If its too sloppy, sputters or whatnot, that's a good way to either negotiate down or just walk away.
And finally, the three "R"s. RESEARCH, RESEARCH, RESEARCH! Knowledge is power, so power up before you go out there. Don't be afraid to say "I'll think about it." and admit your lack of knowledge. The more up-front sellers will point out the bad along with the good. If they say there's nothing weak or wrong or breakable, that's a major red flag. So do your research and learn all you can.