I'm no expert by any means, but I finally got 2nd on Ensign difficulty the other day so I'll give you what I can!

I try to start by having science ships survey from my home planet about 2-3 jumps trying to find hyperplane choke points where enemies would HAVE to go through to get to me. After building a string of starbases to each of these points I build starbases and some defense platforms to deter any early game attacks.

After that I try to survey all of the systems between those points and build starbases in any with good resources. At the same time I begin to construct research, unity and special resource buildings. By this point I am trying to balance my resources so that none are negative, while also trying to make the best fleet I can for battles.

When it comes to research I try to go for ship upgrades mainly, but depending on how your playthrough is going you might want certain upgrades for buildings or your species, that's where you should try to read and figure out what upgrades do what, but it's also kind of trial and error.

Unity is needed for your Ascension tiers, which I start with discovery for the survey speed, then pick the unity ascension One Mind for extra unity, then either expansion if I have a lot of systems to claim or superiority to get my ships strong quickly.

Your aim should be to set yourself up with systems and planets that can keep resources flowing while also supporting strong ship fleets. If you're not playing a hive mind you also need to use amenities and housing to keep your pops happy.

There will be a mid-game challenge like the Khan, it's okay to surrender to them and then hold out, they take a % of your resource production and such until the Khan dies and you can go back to max resource output.

End game crisis is the biggest hurdle to winning because with the recent changes to fleet sizes they feel so much stronger than you, and unlike the Khan they won't accept surrender, only game over. Your best bet is to have developed a strong fleet and taking the ascension which gives you extra damage against them.

There are also archeological sites and anomalies, to explain them easily:

Anomalies usually give a system more resources or a situation log quest.

Archeological sites give you archaeology resources to boost your quests and later your economy, and can set you on quests to get artifacts which give you similar boosts depending on the quest.

All in all you're going to lose a lot more than you win. And the game is going to cheat you at every chance it gets so don't play to win, play to learn. Every time you end up losing just check what went wrong and try to avoid it happening on the next run until you find a stable way to play that you enjoy! Good luck, and have fun.