As in all "What If" stories, this one occurs in an alternate universe where the Punisher decides to kill every hero and villain. With titles like this, the setup is *very* easy.
Hell's Kitchen, years ago. Matt Murdock (prior to being blinded by radioactive waste) is being beaten by a group of neighborhood kids, taunting him with his future alias "Daredevil". A slightly older Frank Castle (who lives in the Kitchen as well) steps in defends Murdock, chasing the kids away. When asked why Frank helped him, he replies that he "hates bullies" and tells Matt to fight back or they'll never stop. Matt tells him of his father's preference that he not fight back. As Frank leaves, he states flatly that his father is wrong.
Now: Frank Castle is a member of a New York SWAT team. He hears that the X-Men and the Avengers are fighting off a combined Brood and Skrull invasion in Central Park. He drives his jeep with his confused partner over to the park to check on them.
When they arrive, Castle sees the aliens being taken into SHIELD custody. He then sees Daredevil lecturing Captain America about the Avenger's behavior. Cap tries to explain that there was no time to check for civilians, but Daredevil points out that a woman and her children are dead because of their action. Cyclops states that it was unavoidable given the situation. At this point the heroes notice Castle running toward them. As he stares at the remains of his family, Cyclops offers an apology.
Castle grabs his gun and shoots Cyclops through the head. He then fires at random targets, hitting among others Hawkeye and Jubilee. Wolverine takes him down, but must be physically restrained by Colossus.
Later Matt Murdock agrees to represent Castle. Given his bereavement status and his military record, Murdock promises to do everything he can to see he's given a fair trial. As he killed "some of this nation's greatest heroes and Cyclops and Jubilee" the judge sentences him to life in prison.
On his way to Ryker's, he is taken on a detour to the Adirondack Mountains by request of a disfigured man known as Kesselring. He is part of a group of individuals who have been severely injured, disfigured, or both in battles between superheroes and supervillains. They applaud him for taking a stand against the "uncaring" heroes and offer him a chance to gain revenge by killing all of them, heroes and villains alike. He offers him a blank check for his armory, Micro for technical support, and as many get-out-of-jail cards as he needs to do the job. Castle agrees and takes up the alias of Punisher.
His first targets are Spider-Man and Venom, who are killed in the sewers. Punisher then sets his sights on the Hulk, or more accurately Bruce Banner. The Kingpin is killed financially and physically. Punisher adds Kingpin's weapons designed to kill specific heroes to his arsenal.
He then pays a visit to Dr. Doom and manages to defeat him using the stolen weapons from the Kingpin but at significant cost to himself. He then raids Doom's castle and acquires his weapons, including a nuclear bomb.
Punisher tricks the X-teams (excluding Wolverine), Magneto, Apocalypse, Juggernaut, Omega Red, Mr. Sinister, Sauron, White Queen and Sabretooth into a confrontation on the moon. Once all of them are together he detonates the nuke, killing all of them at once.
Some time later Wolverine is near an electric power plant trying to drink away the pain of losing his friends and X-family. He recounts how the Avengers died due to a teleporter malfunction; Mr. Fantastic was found dead in the dumpster. All the while he was on a wild goose chase in Japan. Punisher appears and explains that he was responsible for all the deaths and the wild goose chase.
Wolverine attacks Punisher but is quickly impaled with his own claws and is thrown into one of the generators. The adamantium in his body conducts more voltage through him than his healing factor can handle and is reduced to a skeleton. Punisher then goes after Captain America and kills him with a head shot when he distracts him during a fight.
Returning to Kesserling, he is greeted warmly by his society. Kesserling wants Punisher to stay on and take out the next generation of heroes when they appear. When he refuses, Kesserling pulls a gun on him and orders him to stay. Punisher quickly draws his gun and kills Kesserling. He warns the rest of his friends that their pain is long past; they're bitter shells now. He tells them that if they attempt to come after him, he'll kill them all.
Punisher tracks down Daredevil. DD tries to talk Castle out of his vendetta as he (DD) outflanks him at every turn, but he won't listen. Punisher finally gets him close enough and runs a knife through Daredevil's heart. Moments before he dies, DD pulls off his mask to show that not all heroes are the faceless people he's killed over the last three years.
While Punisher regrets killing Murdock (the one person that tried to help him), he has one remaining name on his list. To complete his mission, he turns the gun on himself.
I will grant that Ennis plotted out the deaths of some characters in a believable manner. Cyclops (who almost deserved it), Hawkeye, and Jubilee worked because it was unexpected and at close range. Once the vendetta began, Spider-Man, Venom, Hulk, Kingpin, and Daredevil were also plausible.
However many of the heroes and villains were written grossly out of character and were shown to be nothing short of inept. Punisher killed Dr. Doom with such ease it made me question whether or not it was the real Doom. How he conned the X-villains onto the moon is beyond me. Personality-wise many of these villains wouldn't associate with each other. Very few of them would have the ability to even get to the moon. Can you imagine any of them carpooling? And Wolverine went down like a punk, which is just wrong.
The greatest insult was how Captain America - one of the greatest fighters in the Marvel U - bought it with a simple "hey, look over there" move.
There were a few other deaths they should have mentioned. Thor for instance. How do you kill an Asgardian, exactly?
2.5 webs. For every one thing right, there are two others that really detract from the story. The distinct Punisher elements were great: Frank, Micro, the quirky villains. However when Ennis tries to interact with the other characters, it comes across as uneven. A few fights are interesting, but many of the fights are ridiculously simple. Some plot points make little to no sense. Having the Brood *and* the Skrulls invade at the same time just to have the Avengers and X-Men present to accidentally kill his family? I don't buy that.
Garth Ennis has a reputation for having little use for superheroes, bordering on (if not crossing into) contempt. I'm not sure if this issue provided the basis for that reputation, but you could make a case for it. While even the best can make mistakes, many of the iconic characters are taken out with relative ease at best or with the combat equivalent of "your shoe's untied". The only other character that was well written was Daredevil, who was a little wimpy to be ... well ... frank.