The Reapers, right up until the ending of ME3 spoiled them.
Before ME3 (and still further on if you refuse to acknowledge the ME3 ending, which I'm fine with people doing), i have never seen such an enemy in a space sci-fi before that were so convincing and at the same time such a powerful threat. The Mechanoids from Nexus: The Jupiter Incident, the Nomads from Freelancer and even the Empire in Star Wars still doesn't measure up.
What i really like about the Reapers is:
- They don't accidentally leave themself open or weak (like the Empire did in Episode 6 by luring the rebel fleet to the Death Star and inviting Luke Skywalker on board. I always considered that a bit of a weak conclusion, although given the age of the first SW trilogy, that's acceptable)
- Their technological advantage is overwhelming, but introduced very well in Mass Effect 1+2, and despite them being so different from the other races of the galaxy, they still use familiar principles to fight for the most part (shields, mass effect fields, lasers etc. Only indoctrination and gene-manipulation falls outside of what other races can do).
- They are some of the most awesome foes i have ever seen dialogue with, because they can be so arrogant and get away with it given that they are machines with a dedicated purpose, as well as having WELL well-synthesized voices.
Hearing Sovereign and Harbinger speak about how puny humans are and how our extinction was inevitable was 10 times more convincing than Emperor Palpatine trying to convince us that Darth Vader was lost forever and that Luke Skywalker would bow to him. I was like "Yeah dude, keep dreaming."
Basically, they are the only RPG enemy i can ever say that I've considered myself "fearing" (not for real given that they're fictional, but it's the closest thing i got since on one hand they are so well characterized as enemies, but on the other hand they left the right things unexplained so my fantasy had something to work with as well. That is, again, until the massive blunder that the ME3 ending was).
Also, I'm assuming direct control.