Based on my recent readings of various anti-civilization writers, I think someone should make a game called Anti-Civilization.
It's loosely based on a premise I read in an old issue of Fifth Estate. Basically, some anarcho-primitivist writer said that for whatever variety of hunter-gather society he advocated for, the US (or maybe the North American continent) continent could only support a population of ~1/3rd of what it was currently at.
So, my premise for Anti-Civilization is that it is the modern day, with the political climate being roughly what it is today. You have just been elected president. How do you use your 8 years in office to reduce the US population by roughly 200 million? Of course, your anti-civilization agenda needs to be kept as secret as possible. Because this needs to be a strategy game on par with Civilization, you have to take into account things like body disposal and the ecological viability of your depopulation strategies (for example, you can only dump so many dead bodies into the ocean before you affect the ecosystem in negative ways, and using poison gas to kill hundreds of millions isn't going to score you points for mother Earth).
I think there's also the possibility to introduce an international element, but I'd have to rethink parts of the basic premise. I like the idea of the US and China teaming up to kill off large portions of their own populations under the guise of a false war, but that would end up involving far more conspirators, and I'd have to conceive of ways to incorporate national and international obfuscation into the game.
You could invest in various population control technologies, like converting cattle slaughterhouses to handle humans. ~30 million cattle a year are killed in the US for food. How many of those cattle killing resources can you use while still keeping the rate of cow slaughter high enough to feed the docile, clueless, surviving populace? You can invest in advanced nuclear weapons technologies (like that 100 megaton bomb the Soviets never built) to level cities in false flag operations designed to convince the public into acceptance of martial law, thus allowing you access to more overt actions that would normally appear suspicious.