So this is my first post here. But I was asking myself how to kill at least 51% of Germany's population during the thirty years war. It's often a overlooked part of history here in Germany considering it's effect on it's population and it's mindset for the next hundred years, at least from my perspective. So I want to ask you how we can get from terrible to terrible²? And what effects would that cause for the next 200 years?
You have a number of options:
OK, what we had in the OTL is an overall reduction of the HRE states ranging from 25 to 40%, depending upon a region with some regions having it up to 50% (as in Brandenburg), sometimes even up to 2/3 and in Mecklenburg it fell from 300,000 to 50,000. So achieving your goal on a global scheme is not impossible.
There are few options or, even "better", their combination (
disclaimer: I'm not advocating any form of a genocide or mass death from the epidemics, just follow the script

):
1.
Make this war lasting for a much longer time, say extra 15 - 20 years. Difficult, due to an exhaustion of the sides, but not completely impossible: Peace of Westphalia was signed in 1648 but the French-Spanish war continued until 1659. Admittedly, mostly in Catalonia but the point is that at least two of the main participants had resources to fight for an extra decade. So, take away Portuguese uprising (which forced
Philip IV of Spain to divert attention to that theater) and the French (capture of
Trier,
Alsace, and
Lorraine) and Dutch (capture of Limburg) successes which severed the Spanish Road pretty much putting Spain out of the general war and you still have Spain operating in Germany and supporting the Austrian Hapsburgs. Probably the simplest prerequisite is an absence of Richelieu's efforts to create a modern French army. Taking into an account that it is not quite likely that a person of his intelligence would stick forever to his initial model of paying the subsidies to the foreigners (from Count Mansfield to Sweden) instead of building up a national force, probably his earlier demise would do the trick: it seems that Louis XIII, on his own, was quite comfortable with the old ways. Then, if he dies on schedule, you have years of Fronde and then Louis XIV still being too young to start creation of the French army and to get the results. In a meantime, with the Spain still in play and France much more military passive than in OTL, fighting in Germany continues with the ever-increasing misery.
2.
Increase number of the active combatants. This can be difficult because the
states involved did not have unlimited financial resources. A possible solution would be to have more "free lancers", like Mansfield, raising their own armies and living off the land (with the obvious impact on that "land") or a greater direct foreign, but not French, intervention. For example, a big number of the Polish "volunteers". In OTL Lisowtchiki (otherwise known as the horsemen of the Apocalypse) had been participating on the initial stages of the 30YW but soon after the Battle of the White Mountain due to the complaints of the population (they were killing "even the children and the dogs") Ferdinand paid their salary and released them (most went back home, some went to the service of Maximilian of Bavaria). But their number never was big enough to contribute seriously to your scenario (during Lisowski's raid of 1615 there were 1,200 of them) so you'd need much more of the kind and to let them to stay in Germany for a much longer period, even if without imperial agreement. The realistic numbers would not be enough to make the needed difference but they could contribute noticeably, especially if we assume that the rumors about a good loot would provide for a steady influx of the volunteers during the years of war (say, something in the range of 5 - 7,000 doing their "best" for the 30 years. And if they managed to get interested few thousands Cossacks, even better in the terms of making things worse. More raids from Transylvania also would be helpful.
3.
Epidemics. There were recorded outbreaks of typhus and during the Mantuan War there was an outbreak of the Bubonic plague in the Northern Italy (Milan lost 60,000 out of the 130,000 population, Venice 46,000 out of 140,000, Verona 33,000 out of 54,000; overall losses in Italy were estimated as up to a million). Have them spreading on a larger scale than in OTL and put scurvy and dysentery on the top and you are ending with a LOT of the deaths (possibly, few millions).