There wouldn't be just one strategy. Democrats and Republicans could each choose a strategy. For example, if Democrats won every vote in the top 145 counties, they would have just over 50% of the vote and could beat the Republicans in the remaining 2997 counties (county populations from 2013). Contrast that with the 489 counties that the Democrats actually won in 2016.
Democrats won Washington, DC by a margin of 86% in 2016. If they won the top 233 counties with five sixths of the vote, they could beat the Republicans winning 100% of the vote in the remaining 2909 counties.
There are some problems with this. This is really 50% of population not 50% of the vote. More urban counties tend to have lower turnout among eligible voters and more people who are too young to vote. In some states, felons can't vote. The data is from 2013. Population is changing, shifting from rural areas to cities.
Another issue is that Democrats wouldn't have been trying to turn out voters in DC because they didn't need them. Similarly, they wouldn't have been trying to turn out voters in New York City, Boston, Chicago, or Los Angeles, because they were already winning those states. Republicans weren't trying to turn out rural voters in Texas, Oklahoma, South Dakota, and Idaho for the same reason.
It's not clear where candidates would spend their time with a national popular vote. Even with the electoral college vote, where the tactics are simpler, Donald Trump won in Pennsylvania, Michigan, and Wisconsin. But traditionally, they would have been competing in New Hampshire, Virginia, Colorado, New Mexico, and Nevada--states they lost this time. Different candidates may pick different strategies, as they appeal to different voters.
Of course, in a popular vote election, Hillary Clinton might have spent more time in Michigan, Wisconsin, and Minnesota. She'd have been trying to run up the vote in those states. Or she might have tried to boost turnout in Massachusetts, New York, and California. Potentially, either plan could work.
Should candidates try to motivate their base? For Democrats, that would be urban voters. For Republicans, more rural areas. But there are Republicans even in urban areas and Democrats in rural areas.
Should candidates try to appeal to undecided voters? They would be located mostly in suburbs. But they're a double-edged sword. Maybe you convince them to vote for you. Maybe you chase them to your opponent.
Currently Democrats' concentration in cities hurts them, wasting votes in the District of Columbia as well as New York and California. With a national popular vote, it would be an advantage. Republicans would have to go farther to reach their voters while Democrats could concentrate on cities. Perhaps Republicans might develop an urban/suburban strategy to replace their rural/suburban strategy.