Disease
I don't think I have to emphasise how influential Disease has been in History. From the Black Death setting back Europe by decades, to the Columbian Exchange which killed countless Native Americans. I'm not sure how Humankind would handle invisible factors like the Immune System of Natives building up defences against local Diseases, while being susceptible to those from other Continents, for example, if such a Mechanic was to be put into the game. How often should Plagues appear, how much impact should they have, on say Food, Industry, Money, Science, Stability and Fame, and how factors like local customs ( such as not burning the dead ), poor Sanitation, lack of research into medicine, and crowded cities can be implemented and impact your Civilization and Culture. Remember that oftentimes, disease has more of an impact on stability and morale than actual population damage.

There are also many gameplay-related decisions I can think off - should Diseases be common, remain isolated in a province most of the time, with very few spreading rapidly and causing damage? This could make players put down their guard if diseases are quite common and unlikely to develop into a plague, reflecting the attitude most ancient leaders had towards small breakouts. Also, this could in turn lead to many factors, involving trading ( will traders avoid disease-stricken provinces ), tourism ( in late-game ) and stability of individual cities. However, plagues should also help the people develop immunity to the disease, improve medicinal practices and sanitation, and allow factors such as religion or leaders to shine in such dark times, increasing fame.

Religion
Religion is also something with enormous impact on history. Everything from the Crusades in the past, to discrimination and biases now, have revolved around religion. Will Humankind follow the example of Civilization VI, where religion is largely spread thanks to missionaries and apostles controlled by the government, or should it have a random factor, where leaders can implement policies to support it's spread, but missionaries are by large random, perhaps affected by the population of faithful? Will military victories affect faith, and how much fame should faith provide? Countries like Israel and Vatican City are famous because of their religion, and attract many tourists because of it.

Natural Disasters
In one of the screenshots, we see Mount Vesuvius. It's famous for destroying the Roman town of Pompeii. Natural Disasters, like that of the eruption of Eyjafjallajokull that cause chaos in the airline industry of Europe, or the 2011 Tohoku Earthquake in Japan, can cause great infrastructure and population damage while also decreasing stability and industry. However, should it be record-breaking, and the leaders able to overcome them to lead their citizens to a new golden age, it should also be able to increase fame and tourism, perhaps even religion. I was thinking of global warming as well, like the Gathering Storm DLC of Civ VI, but I feel that Humankind is more past-centric than future, and thought that it would be a mechanic that would be better added as part of a DLC after the game is released, if at all. 

Diplomacy
As the saying goes, Might makes Right. Like how the US used nuclear diplomacy during the Cold War as it held nuclear monopoly, having a great military is taxing on your treasury but provides great intimidation factor that can be used to expand, but a standing army can also be used to suppress people in politics. While I see tactical battles being great for ancient times and World War-like battlefronts, what about trade embargoes and tariffs, diplomacy, and nuclear bombs that hold such great power in modern politics? Nuclear bombs irl are basically for self-defence as no ( sensible ) nation would want to start World War III and end humankind. However, in-game players hold no such qualms, so unless they have significant ramifications, are something that will be hard to balance properly.

Agreements & Alliances
This is something that Civ VI has but doesn't do well, as the players can often ignore them. However, these agreements hold great influence in real life. NATO and the Warsaw Pact held great influence during the Cold War, and the United Nations, European Union, Geneva Convention, and NPT continue to hold sway over world leaders today. Hopefully, Humankind can better reflect them, but as I mentioned before, it seems Humankind is more past-centric, but they shouldn't ignore such matters.

This is my personal opinions, thoughts and suggestions. Feel free to leave constructive feedback. 

Religion is definitely crucial here, but i really hope it's not like in Civ 6 where you make these ridiculous apostole fights

Assuming a system similar to Endless Legend, maybe disease could be shown similarly to how security against espionage was in that game, but instead of security its immunity. Things like an apothecary, a sewer, and a hospital could increase immunity, as could special heroes, events and decisions like developing herbal medicine or encouraging inoculations, or empire plan type policies like quarantines. A city hit by disease would be marked with a malus that disables x workers for x turns and decreases stability, before having a (50 minus difference in immunity levels) percent chance of hitting another city with active trade routes. 

For religion, I think it would be difficult to implement a passive religious system into a game about controlling the story of human history. And without a DLC, there has been no evidence of some kind of faith/ religious resource for controlling religion so far. I could see religion as some kind of in game event about balancing persecution with tolerance, or maybe as some kind of quest that requires certain kinds of achievements to complete by the medieval era, but unless the game is significantly different from the system in Endless Legend I don't see how it could be put in place as a fully fleshed out religion.

Natural disasters are something that lend themselves to the random event system, where claiming the Mt Vesuvius tile gives its own bonuses but also threatens triggering an event to destroy a borough or several buildings. I agree though that global warming is hard to put in place while stopping at modern day.

You make a good point about warfare and diplomacy. I could see the economic warfare like embargos used by the Roving Clans in EL being available in the late game in Humankind. As for nukes, maybe some kind of high cost in influence points/ diplomatic consequences for their use?

For alliances, treaty organizations are definitely something I'd want to see in the game. Maybe it could be a late game diplomatic option where the factions could share x% of their fame or something, at the cost of having to spend influence and having the same military stance towards other factions?

Having not played Endless Legends before, I am unable to tell how balanced or realistic such a mechanic would be. However, it does sound quite sound. Speaking about 'Special Heroes', it reminds me of the Great People Mechanic in Civ 6. I have nothing against that except for most Great People not having especially unique Bonuses. In history, most religions spread due to either missionaries or passive integration. However, these missionaries randomly appeared ( perhaps a random event ) and shouldn't be 'created' per say by leaders. Again, natural disasters are not difficult to integrate into most strategy games, and it is likely that they will follow their previous games. Nuclear bombs have been very influential in recent human history, especially in during WWII to present-day. I suggest that simply having a nuclear bomb provides benefits to diplomacy with countries without them, giving a passive benefit that staggers according to the number of people who don't own one, while using it will enrage all of the other leaders. This carrot-and-stick method will work until most leaders have them, after which... I have no clue.

About religion: didn't you think about additional mecanic "spread foreighn religion in own country"? There are many examples in history when leaders took and spread foreight religion for some political or personal reasons, sometimes with fire and blood. There isn't such mecanic in Civ games but there is a mecanic with such idea in CK II

FrostEmpyrean wrote:

Having not played Endless Legends before, I am unable to tell how balanced or realistic such a mechanic would be. However, it does sound quite sound. Speaking about 'Special Heroes', it reminds me of the Great People Mechanic in Civ 6. I have nothing against that except for most Great People not having especially unique Bonuses. In history, most religions spread due to either missionaries or passive integration. However, these missionaries randomly appeared ( perhaps a random event ) and shouldn't be 'created' per say by leaders. Again, natural disasters are not difficult to integrate into most strategy games, and it is likely that they will follow their previous games. Nuclear bombs have been very influential in recent human history, especially in during WWII to present-day. I suggest that simply having a nuclear bomb provides benefits to diplomacy with countries without them, giving a passive benefit that staggers according to the number of people who don't own one, while using it will enrage all of the other leaders. This carrot-and-stick method will work until most leaders have them, after which... I have no clue.

The Idea that releigons/great prophets/missionaries are generated by random events seems like a great idea! Perhaps instead of players just "mechanically"  striving to create a relegion, a random event in a nation/city with great cultural production/significance could cause a faith to form, with it's character depending on the "Traits" the founding nation had during it's creation/generation.