The galaxy is trapped in an endless cycle of extinction. Every 50,000 years an ancient machine race invades and with ruthless efficiency wipes out all advanced organic civilization. They leave behind only the scattered ruins of technology, destroying all evidence of their own existence.
It shows its age here and there in terms of gameplay, like how there's only like 3 interior templates that you might come across in the uncharted worlds, how driving is really boring and tedious, or how enemies have the same 3 lines which they repeat over and over again. And the inventory system is really, REALLY unintuitive.
Also the first few hours of the game drag on for too long, and there's a lot of information dump, which feels very cheesy and generic (all the talk about having to save humanity, blah blah). I personally have a bit of a problem with how aliens were designed to look and feel appealing rather than actually alien, except for the baddies, of course. Every race is bipedal and humanoid, and speaks english. Now it's nothing different from most other sci fi universes and games, but it feels more prominent in this game because of how much of the lore is provided to you, were it through dialogue or codex entries.
But hell, it's a god damn good game, and the main storyline really shines once you get to fly Normandy around the galaxy.