I hate all the modern live action adaptations of animated characters right off the bat - so I would have nixed the projects to begin with. In my book live action is always inferior to animation. There were no redeeming traits based on the trailer!
If I was to make a "for adults only" Powerpuffs all grown up series, I'd put them as college age students who still retain the naivete and positive attitudes of the original Powerpuffs. I'd have them go up against dysfunctional versions of other CN superhero properties, dealing with the millennial-generation issue where every major institution is a thoroughly corrupt and/or incompetent version of itself. Think one of those bad future Justice League settings.
The Powerpuff girls would use their boundless optimism and ultra-super-powers to fight the forces of depression and the evil in the hearts of everyone, including their own villain roster - a certain monkey super genius might be advising the president, for instance.
I'd probably do a crossover with Totally Spies, Ben 10, or even Uncle Grandpa. Real nostalgia trip stuff. We'd definitely do a Powerpuff Girls Z episode. But no matter what, the girls would be positive and wholesome even if the world around them is crappy and terrible, which was a core element of the original show.
And if course we would have the OG voice actresses involved, with Craig McCracken and Lauren Faust in executive positions!