We've previously established at some length that -- at least allegedly -- there are things happening at the bottom edge of the world that could be good fodder for a game. The problem, however, may be that there's just too much happening in Antarctica to make a plot hang together: a tidy bit of irony considering that the place is supposedly nearly devoid of sentient life. We've got disappearing (and reappearing) scientists, hidden Nazi fortresses, unexplained geomagnetic anomalies that could signal a gateway to the hollow earth, potentially alien microbes, antediluvian artifacts, and at least one geographic and media cover up that reaches the highest levels of the U.S. intelligence apparatus. And that's just the tip of the iceberg. Pun intended. With a menu this diverse, how do you choose which way to go? No complex advice, here. You just need to pick a few favorite elements and start knitting your conspiracy together. Then let your PCs grab a thread (a yarn?) and unravel the whole thing.
Let's go with the alphabetical approach.
Alien Encounters
So let's assume for a moment that some kind of alien life is at the center of our polar conspiracy. Small microbes or alien organisms with exotic biologies -- maybe from Mars, maybe just the product of strange evolution -- are freed from their eons-long isolation in Lake Vostok as a team of Russian scientists breaks through the last layer of ice. Their expedition? Intended to be innocent scientific inquiry. They are nevertheless unprepared for the affects the microbes have on them. Perhaps they mimic the affects of a movie zombie outbreak: a rage virus, or a microbial quasi-undeath. Or perhaps the microbes wreak strange physiological changes upon the scientific team: exposure makes them degenerate mutants, tentacled semi-human monstrosities, members of a long-slumbering alien hivemind, or the first members of a new breed of superhumans.
You can build an entire adventure around an investigation into the suddenly silent Vostok Station by fellow scientists from another Antarctic research station -- a good basis for mystery (perhaps Gumshoe?) or horror (perhaps Dread?). A slightly different game presents itself if your PCs are just part of the crew of a cargo mission sent to the Vostok site to retrieve water samples for further study in Moscow, and find themselves trapped on the long flight to civilization with the victims of a poorly understood alien infection or a subtle (and perhaps intelligent) xenobiological being.
Or skip right over that: your PCs know that something is wrong, and are sent in to secure samples from the now-hostile (or perhaps just subtly corrupted) scientific team, and return them to civilization for study. Or maybe they're just on black ops "cleaner" team sent in to ensure that the unexpectedly dangerous alien presence is destroyed before it can spread and wreak havoc on the rest of the world. Probably a good game for Savage Worlds, GURPS, or the now sadly out of print d20 Modern.
And all this assumes that the alien presence in Antarctica is subtle -- insidious.
Perhaps the thing hidden beneath eons of accumulated ice is something larger -- more obvious. Maybe it's an alien colony ship sent off course by an errant meteor impact, a probe sent to study earth from a post-human future, a dormant Wellsian Martian tripod, or really any kind of magnetic macguffin you care to hide beneath the surface of a subglacial lake. Set your game immediately post- (or during) WWII, and your game can be an espionage-filled thriller as your stalwart heroes -- no doubt working in the shadows of 1947's Operation Highjump -- must race the Nazis to an ancient, powerful alien weapon whose location is revealed by an allegedly suppressed version of the infamous Piri Reis Map. Let the Nazis get what they came for, and your game can be an alternate history World War III driven by a combination of atomic weapons and only partially understood alien technology. Or don't: Operation Highjump's discovery and confirmation of nonhuman intelligence can just be your way to explain the existence of a contemporary game's ultra secret black ops intelligence agency, or the spark of an interstellar war that most of humanity is unaware Earth is even a part of.
And we haven't even broached the possibility that all the Antarctic weirdness really springs from the fact that the icy frontier is actually Atlantis.