I have to go with Nathan Drake. 

Over the course of four games hes killed 1000's of people. 

Hes really gonna rack up the body count in Uncharted 4.

Who do you think has the highest kill count?

EDIT: Lol I know Samus and Chief has killed millions but when I say kill count I mean in a realistic sense(as dumb as that sounds). Nothing with goombas or aliens. For example Max Payne. His kill count is probably in the 500s.

Mario.

The mushroom and turtle stomping scourge of life that is Mario.

Mario cause across decades of gaming, he killed who knows how many creatures

So 4/4 Mario in replies so far lol

IT'S A ME.

My character in Civ 5, armed with nukes, wiping out other Civilizations.

As a more serious answer.

Master Chief. Responsible for killing literally Billions when he wiped out The Flood.

Commander Shepard has canonically achieved one massive genocide. You can do a second one in Mass Effect 3, and I'd say no other videogame character can come close to this.