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Outside of godlike beings (Timelords, Stargate Ancients, Q, Chaos Gods, etc) I'd give it to the Borg, Necrons, or Tyranids.
The Borg's ability to assimilate almost any species or technology makes them a huge threat. Even if a species is more powerful than the Borg, all they have to do is assimilate a few of their ships, weapons, and people, and they can enhance the technology far beyond its original capability, while becoming virtually immune to their enemy's weapons.
The Necrons that have been seen are just a scouting force, and they can wipe out whole Imperial Guard regiments or Space Marine Chapters. Anything the Imperium, Eldar, Orks, or Tau could throw at them wouldn't stand a chance against their full forces.
The Tyranids make the Flood look like a freaking tapeworm infection. They've consumed whole galaxies and number in the untold quadrillions. The Imperium suffered massive losses to only a small percentage of their forces. Nothing (except the Necrons) could withstand a full assault by the Tyranids.