Although the Browning M2 has a very high strength requirement, its in-game firepower is the most powerful of any machine gun. The M2 has the longest range of any automatic weapon, but its damage and rarity of ammunition are dwarfed only by the MEC Gauss minigun.
The Browning M2, loaded with extremely rare .50 cal, made of depleted Uranium, is a devastating weapon, even against robots, who are insusceptible to conventional firearms.
The M2 first appears during the St. Louismission, carried by at least two guards in the super mutant Fortress in the far north of the map and two guards in the area around it. They have .50 Depleted Uranium (DU) rounds and can easily kill your entire squad. One mutant in the entrenchment wield the gun with ordinary round in it.
Two mutants in a building on the right side of the Jefferson map carry this gun. Unlike the St. Louis mutants, they only have regular .50 rounds and (probably) won't tear your squad apart with a single burst. One mutant with the gun guards enter to the tunnel. Another mutant with Browning M2 stands in the center of a callow, near the final objectives.
There are several super mutants with this weapon in Kansas City. One of them snipes from the tower (opposite the West gate), other take part in South Gate assault.
Sometimes, during random encounters with super mutants, a few of them may carry this gun. Typically they have a small amount of regular .50 rounds for it.