Nobody in the world could put that ball back into play. When Isner shifts his body weight, allowing him to explode as far into the court as he does to strike his serve, he accesses incredible angles.
A slice serve is typically cut off by stepping diagonally to the ball, which stops the ball from spinning too far away from the court. But Isner is able to land his slice shorter in the service box—without reducing his velocity all that much—making it impossible to return unless you're camping out in the doubles alley. Isner’s height also causes his slice to bounce higher than most kick serves.
Much like his slice in the deuce court, Isner can hit a nasty kick serve in the ad court, which bounces over most players’ heads and takes them out into the doubles alley.
Now there is another dilemma. If you protect the wide delivery against Isner on either side, you give up the middle of the court, which is naturally a higher percentage serve to hit since the net is lower—36 inches tall compared to 42 inches at its highest out wide. Camp out wide for one serve, and Isner can hit another one at 140 m.p.h. down the T.
Harrison certainly recognized what he was forced to deal with on Sunday. When he broke immediately to start the second set, that was an accomplishment in and of itself.