For the uninitiated:
The Prime Directive, also known as Starfleet General Order 1, the Non-Interference Directive, or the principle of non-interference, was the embodiment of one of Starfleet's most important ethical principles: noninterference with other cultures and civilizations. At its core was the philosophical concept that covered personnel should refrain from interfering in the natural, unassisted, development of societies, even if such interference was well-intentioned. The Prime Directive was viewed as so fundamental to Starfleet that officers swore to uphold the Prime Directive, even at the cost of their own life or the lives of their crew.
The fundamental idea is that you can have the best of intentions but still fuck things up, so you shouldn't intervene even if you think you have good reason. This strikes me as the best counterargument to what constantly sucks liberals into imperialist adventures -- the tempting idea that "someone has to do something," or "if we stand by and watch bad things happen, doesn't that make us complicit?"
The Prime Directive has a simple answer to that: it's likely you're going to make things worse, and what right do you have to intervene, anyway? The Star Trek libs in your life will have to recognize this principle, and the closer you look at U.S. foreign policy, the more sense it makes. It's also a natural lead-in to talking about how often the government lies to manufacture consent for wars.
And what are they going to do, say "that's a fictional story and the real world is different"? These are the folks who are comparing Lev Parnas to Neville Longbottom or some shit.