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Even if you don't have to knock them all out at once, it's still helpful if they're in an open place. You can knock out several guards from a distance with a single sleeping dart.
Of course, it won't get any worse if you want to kill them instead of knock them out, but for killing, there are a lot more possibilities, so it's less important for a combat playthrough. For combat, I assume doppelganger is pretty helpful, especially when it can fight back and/or assassinate targets as well.
If you invest in Domino, I would also recommend getting the instant sleep dart upgrade as quickly as possible. I've never used Doppelganger, but I read somewhere that you can Domino-tie it to your enemies, which sounds like a hilarious dilemma.