If one wants to be precise, one should measure deadly harm not in deaths (past people were still going to die if lung cancer didn't get them), but in quality-adjusted life years, pretty much the best unit ever.
And no, I'm not sure assassinating CEOs would help, unless it was public enough and effective enough to actually dissuade people from leading the company in any capacity. Bombing factories would be much more efficient.
Should the fact that a fair number of people actually enjoy smoking be figured into this?
The man-made object responsible for the most deaths worldwide is the tobacco cigarette. It isn't even close.
Tobacco kills 443,000 Americans a year and 5 million people a year worldwide. This is more than the total number of people killed by cars and firearms combined. Cars kill about 32,000 Americans each year and 1.3 million people worldwide, while firearms kill about 32,000 Americans each year and "several hundred thousand" people worldwide.
100 million people were killed by tobacco in the 20th century. This is more than the death toll from World War 1 (17 million) and World War 2 (50 to 70 million) combined.
From a strictly utilitarian perspective, would there be anything to be gained by, say, starting a campaign of assassination against executives of tobacco companies?