Infectious disease...

One of frequently asked questions about history is how a few hundred Spanish Conquistadors managed to bring down entire empires.

And well... They did not. What really brought down those empires were the new infectious diseases that the Europeans brought with them, that the native populations had no immunity to. Smallpox killed more natives then all the combined artillery, firearms and cavalry of the Conquistadors ever could.

There is no reason to assume that the same would not be true with the alien species in Mass Effect.

The Humans and Turians make contact. Go to war right off the bat, and unwittingly give each other a whole slew of diseases that neither have immunity to. Suddenly, entire populations are being ravaged by epidemics that they are not familiar with at all.

And the same goes for any of the species of Mass Effect, except maybe the Quarians.

The Krogan especially would have been already wiped out by diseases given to them by the other species. Considering they basically have no medical science of their own. How many Krogan doctors do you think there are?