The men encountered Sherrell Paul, 39, at the top of the stairs and opened fire, striking her eight to 10 times, said Philadelphia Capt. James Clark. Paul, 35, heard the noise and ran to the hallway, where he confronted the intruders and was shot multiple times.
The gunmen then fled the building and jumped into a dark-colored car that was waiting out front, driven by a third person.
Paul was pronounced dead at the scene. His wife was taken to Temple University Hospital, where she was in critical but stable condition Monday night.
The couple's young sons, who were awakened by the gunfire, were unharmed. They called 911 after discovering their parents in the hallway outside their bedroom, police said. They are in the care of extended family members.
At a news conference, Philadelphia Capt. James Clark said police are at a loss as to a motive in the shooting.
"[John] seemed to be a good, upstanding person," he said. "A family man, someone who was not known to police, who has never been known to police. It's a mystery to us why they were targeted."
Clark said it was possible that the gunmen had the wrong house, and that the couple was attacked because of a case of mistaken identity.
Police do not believe the Pauls knew the gunmen, but there was no sign of forced entry into the house. The gunmen went in through the front door, which was guarded with a metal grate and several locks.
"The locks aren't the best, so we don't know whether they were picked or they possibly had a key," Clark said.
Police also do not know whether anything was taken from the house, which did not appear to be ransacked.
"We don't know what they were looking for," Clark said.
Police found a trail of blood outside the home and are searching area hospitals for one of the gunmen, who they believe may have been shot and injured during the confrontation. Police do not believe John was armed, but during the struggle in the hallway, one of the gunmen may have accidentally shot himself or his accomplice.
Clark asked anyone with information to call the homicide unit at 215-686-3334. A reward of up to $20,000 is being offered for information about the killing.
Paul and his wife, who had no criminal records, both worked in the health-care field, though Paul recently had been laid off, Clark said. Sherrell Paul, who also is known as Sherrell Rhine-Paul, wrote on her Facebook profile that she attended West Catholic High School and that until last year, she worked for Mercy LIFE, an elder-care program that provides medical and social services.
Several people who stopped by the house Monday and described themselves as relatives declined to comment.
Residents of the area said the neighborhood had grown steadily worse in recent years. There are several abandoned houses on the Paul family's block, and one neighbor, who declined to give his name, said drug activity seemed to be increasing on several corners.
Marrero described Paul and his wife as friendly, and he said they had lived in the house for at least three years. He was shocked to hear the news.
"These weren't people who were running amok in the streets, starting trouble," he said. "These are good, family-oriented people who were keeping to themselves, going to work, doing the right thing."
Contact staff writer Allison Steele at 215-854-2641 or asteele@phillynews.com.