Easiest place to get this done is actually the Death encounter: the Reaper himself counts as an Assassin, and his final battle is him entirely alone. This works well because Reaper's Arrow can't be targeted, so you would otherwise need to kill everyone else and isolate and weaken an Assassin first.
If you save all three charges for him, you should only need to take off about 1/4-1/3 of his life bar before you can spam Reaper's Arrow and kill him. Achievement proc's when he's dead.