Guentzel cut Philadelphia's lead to 4-3 at 12:36 of the third period when he tapped in a pass from Letang on a power play. Ruhwedel tied it 4-4 at 12:54 with a one-timer.
Letang stole the puck from Claude Giroux at the other end and looked toward Crosby on a 2-on-1 while scoring five-hole. He has scored 30 overtime points (eight goals, 22 assists) in the NHL and passed San Jose Sharks defenseman Erik Karlsson (29; seven goals, 22 assists) for the most by a defenseman.
"Of course, you want that game, that memory to be a win." Letang said. "You don't want to remember [Crosby's] 500th goal in a loss, especially to a rival like this."
Giroux gave the Flyers a 1-0 lead at 13:47 of the first period on a snap shot from the slot.
Dominik Simon tied it 1-1 22 seconds later by tipping a shot from Marcus Pettersson.
Crosby gave Pittsburgh the lead at 16:34 with his 14th goal of the season, a one-timer from a sharp angle off a pass from Evgeni Malkin. Crosby is the second Penguins player to score 500 goals, joining Mario Lemieux (690), and the 46th NHL player to do so.
The goal was Crosby's 50th against the Flyers, his most against any team.
"It's been an incredible journey for me, to be the coach of the Penguins and, in particular, to coach Sid," Penguins coach Mike Sullivan said. "I've had the privilege of seeing a fair amount of milestones over this time here, with respect to Sid. I thought tonight might be the most special."
Laughton tied it 2-2 57 seconds into the second period on a wrist shot from the slot. He has scored eight points (four goals, four assists) on a six-game point streak.
"At the end of the day, if you don't win games, it doesn't really matter about the points," Laughton said. "We just have to figure out a way to find a way."