I was thinking about the deadliest conflicts in the history of the Alpha Quadrant and two came immediately to mind - the Dominion War and the Borg Invasion of 2381.
The Dominion War's often referenced as one of the bloodiest conflicts in history, bringing down one of the Quadrant's major powers (the Cardassians) and with catastrophic death tolls for all parties involved. Though no hard numbers of total casualties for the Dominion War were ever given, in "Statistical Probabilities" the genetically engineered think tank estimates 900 billion casualties if the war continues - a huge number, even if just a future projection.
The Borg Invasion of 2381 destroyed 40% of Starfleet's forces and resulted in 63 billion killed, not to mention the devastation to entire planets and destruction of the Borg Collective.
What's crazy to me is that these two events happened within six years of each other! The two (to my understanding) deadliest conflicts within six years of each other. I mean, especially for the UFP, that's just a lot to take.
Has there ever been anything even coming close to these two conflicts in Alpha Quadrant (or, for that matter, galactic) history?