You're going to need a couple of things for this: Access to the arcane university, a common level soul gem, and you must know a drain health spell.
I found that the item duplication cheat is handy after this because the weapon only has 16 uses.
Go to the altar of enchanting, pick any weapon and select the drain health. You can put the magnitude to 100 for 1 second, so theoretically their health will start regenerating straight away, but by also putting fire/shock/frost damage on the weapon, (even just 1 point would be enough) you essentially in that one blow drain their health to death so they can't recover.
This isn't even expensive so make a couple of back up if you want.

So now go forward and behold as the entire of Tamriel and Oblivion trembles in awe of your weapon of instant death (ironically the weapon is only worth around 600 gold).

I found it most effective on the Katana that the blades use, mainly because it's quick and a bit longer than other weapons, so if used right you never get hit.