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Regarding politics, some immediate thoughts that relate to 4x and grand strategy games:

• History is cyclical, we go in and out of golden ages.
• Even when you prioritize cultural or scientific victories, you cannot neglect your military. You can't have Hollywood and universities without keeping up a strong military. Yet the factors are intertwined, so strong military without science and culture means that your country will also fall behind.
• Spreading your religion and culture to other countries can give you a military advantage.
• Avoid fighting wars on 2 fronts.
• When you're too far ahead of everyone else, they will gang up on you.

But most importantly, avoid falling for the ludic fallacy. Games can model real life and teach us things, but the map is not the territory. History is greatly influenced by black swan events that cannot be modeled in games. Getting too good at games can give you a false sense of security, believing that the world is more predictable than it really is.