Murray's victory came not long after his potential quarterfinal opponent, Tsonga, retired with a left knee injury while trailing Ernests Gulbis 3-6, 6-3, 6-3.
Darcis withdrew a few hours before his scheduled match against Lukasz Kubot of Poland. He said he hurt his right shoulder while diving for a shot in the first set of his win against Nadal.
"After the match, a few hours after, I start to feel so much pain, I couldn't sleep that night," he said. "I saw the physio, the doctor, yesterday. They did a good job. It's a little bit better today. But no chance I can play."
Darcis had become an overnight sensation after beating the eight-time French Open champion.
"I was playing maybe the best tennis in my life here," Darcis said. "Not to go on the court today, it's maybe the biggest disappointing thing I have to do."
The tournament also lost 2002 champion Hewitt, who was ousted by 189th-ranked German qualifier Dustin Brown, 6-4, 6-4, 6-7 (3), 6-2.
The dreadlocked Brown, who switched nationality from Jamaica in 2010, was in tears after beating the Australian.
"I cried like a little girl," said Brown, who has played mainly on the lower-tier challenger circuit in 2013 and had never won a match at Wimbledon until this year.
Ninth-seeded Wozniacki slumped to a 6-2, 6-2 loss to 196th-ranked Czech qualifier Petra Cetkovska, continuing her disappointing run since finishing 2011 as No. 1.
The Dane said she slipped during the match and her foot was bothering her.
"I didn't feel 100 percent out there after I slipped," she said. "I overstretched the foot a bit."
In another women's match, Canadian teenager Eugenie Bouchard picked up the biggest victory of her career, beating 12th-seeded Ana Ivanovic, the 2008 French Open champion, 6-3, 6-3 to reach the third round.
Isner, the 18th-seeded American, retired during his second-round match against Adrian Mannarino of France after only two games.
Isner took a medical time out during the second game and a trainer taped the knee. But he was clearly hobbled and decided to quit after serving the first point in the third game.