The M6G is quite useful against most sparse targets that are encountered throughout diverse combat. Enemies such as Grunts and Jackals can be quickly dispatched with one well-placed shot to the head and enemies like Drones and members of the Flood can be dispatched in as little as 1-2 well-placed shots (though other, more effective weapons are suggested against the Flood). The same can be applied to unshielded Brutes with one well-placed shot to the head.
The M6G's high-caliber rounds give it the ability to stumble non-berserk, unshielded enemies. This is most effective fired at the feet, when enemies like Brutes suffer the longest injury recovery time.
Equipping a Plasma Pistol as your secondary weapon is an excellent way to eliminate practically any target in your path. An overcharge shot (or several bursts of standard fire) from the Plasma pistol will eliminate any shields, leaving your target open for a single, final head shot from the Magnum. Due to the near ubiquitous Plasma Pistol usage by lower-ranking Covenant, this is an excellent way to save ammunition.
Wielding a pair of Magnums performs quite well against shielded targets (and looks rather intimidating as well), but is restricted due to their rate of fire and the lack of accuracy at range. Dual-wielding a Magnum with other weapons such as an M7 SMG or a Plasma Pistol is also quite effective as the SMG depletes shielding quickly, while the Magnum finishes the target off; a Plasma Pistol's charged shot will completely drain any shielding system allowing the Magnum to perform the lethal head shot.
In Reach, the faster rate of fire means that it can be used as an effective close quarters weapon as opposed to a back up weapon (and is in fact often used instead of the MA37 assault rifle it usually is paired with in loadouts). Fire at opponents' body to drain their shields and use the remaining shots at their head.
The reload on the M6G is fast even if the magazine is completely empty. If your target is almost dead and you're about to run out of ammo, empty the magazine and reload.