Smoke bombs are your friend. The place I got the No Hitter achievement was at the Vatican walls - specifically the area where there is a horse. There are exactly 10 guards there and you are notorious so there's no need to get their attention.

Once they've surrounded you, use a smoke bomb and then equip the hidden blade to quickly dispose of them. When assassinating, make sure that you aren't in fight mode so that you can take out two guards at once. Being in fight mode causes Ezio to single out enemies thus resulting in an inefficient use of the smoke screen. Once the smoke has worn off, immediately throw another smoke bomb and begin assassinating once more. Just rinse and repeat until all ten guards are dead.

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