i suppose flares MIGHT help IF the increase in frontal area is compensated be the reduction in drag.... i'm not sure if that's mathematicly possible, because frontal area is more important than Cd in cda... that is, nocking off a mirror is easier than reduceing your Cd by 0.01...
however on some cars the bodywork curves in near the bottom and exposes some of the tires
like this
in this case "fender flares" down there won't really add frontal area!
here's another thing to think about
the toyota IQ... 0.299 Cd... those bumps are there for a reason
i think a lot depends on what happens before the fenders... older more square cars, or cars with a shorter nose, might have less attached flow before the wheel arches so perhaps there these flares might help somehow....
just some guesses though.