I'm getting overwhelmed by the tech tree. I think I grasp the first 2-3 layers, have my go-to techs, got a feeling of what to pick first, and what I can postpone till later.

However, the upper layers are just too big with too many techs scattered across the quadrants. I'd appreciate some pointers.

What are the mid- to late-game techs that change game significantly that I should almost always pick earlier? (Think something similar to Galactic Commodities that open a market on level 2). Any "hidden gems" - techs that don't sound impressive but are very good in practice? What modules should I rush to be ahead of opponents?

Mid game is usually dominiated by techs that fit your galaxy.  In the exploration tree there is a tech that offers +40% science, dimensional folding, go for that, vacuum for repair bots on your escort ships is another one.   Also you want the extra CC tech, its the military tech in the farthest left in tier 3..  After that tech you should be researching tier 1 mediumd and tier 2 medium ships.  Then get the upgraded versions that are techs above them.  

In the economy quadrent focus on researching tech that gets you new resources.  If you mouse over you can see the tech to get you access to Adamantum, antimatter, Orchilox, and the purple resource.  Focus on the techs that get you the planets you have access too in your empire. 

@plutar

Thanks!

> Then get the upgraded versions that are techs above them.

I have a related question: should I research bigger ships first or upgraded hulls for smaller ships that I already have?

@mamarider

> I am actually super confused with late game food techs.

Yeah. Also, it's surprising that so most early game food/population inprovements are in the Empire quadrant of the tech tree, but many late-game are in Science quadrant.