(CNN) -- Roger Federer is out, Juan Martin del Potro is down -- that leaves Novak Djokovic as the only U.S. Open champion left in the men's draw as the season's closing grand slam reaches the final four.
And, after being beaten in three punishing sets by the Serbian, del Potro believes five-time major winner Djokovic is the favorite to defend his title in New York come Sunday.
The world No. 2 still has to get past dark horse David Ferrer in Saturday's semifinals before he can line up against Olympic champion Andy Murray or Federer's conqueror Tomas Berdych.
It will be the first major since the 2004 French Open where either Federer or Rafael Nadal have not featured at this stage.
Del Potro, the last man other than Djokovic, Federer or Nadal to win a grand slam when he triumphed at Flushing Meadows in 2009, had no doubt about his tip for victory after losing 6-2 7-6 (7-3) 6-4 in Thursday's quarterfinal.
"It's not easy when you fire your best weapon and the other guy returns all the serves. It's difficult when you have in front of you a warrior," the Argentine seventh seed told reporters.
"He's playing better and better every day. He's the favorite to win this tournament. I saw him playing at a very high level for the three hours in the match and he has intensity to win all the matches."
Djokovic has yet to lose a set in five rounds, and the Australian Open champion had dropped only 20 games before being tested by the 23-year-old del Potro -- who beat him in the Olympic bronze medal playoff last month.
"Even though it was a straight-set match, it was much closer than the score indicated," said Djokovic, whose only other reverse against Del Potro came last year when he retired hurt in the Davis Cup semifinals following his epic rain-delayed win over Nadal in New York.
"I was lucky in the second set to get out with a two-set advantage. We played some incredible rallies and incredible points."
Djokovic lost to Ferrer at the end of last year at the ATP World Tour Finals, but that came following a long season and he was a shadow of the man who had leaped to the top of the world rankings by winning two grand slams.
The Spanish fourth seed has reached the New York semifinals for the first time since 2007, winning a five-set epic against Janko Tipsarevic on Thursday to deny Djokovic's compatriot his first last-four appearance at a grand slam.
"He's one of the biggest competitors we have in the game," Djokovic said of Ferrer, who he leads 8-5 in career meetings.
"He has been one of the most consistent players on the tour. He plays great on every surface. You need to earn your points against him."
Ferrer dropped his first sets of the tournament as eighth seed Tipsarevic came from behind to lead 2-1, and the 30-year-old had to overcome a break down in the decider before finally triumphing 6-3 6-7 (5-7) 2-6 6-3 7-6 (7-4) in four and a half hours.
"It was a very emotional match, one of the best emotional matches of my career," Ferrer said.
"My opponent, he also deserved to win this match. In one tiebreak it's a lottery, and I had luck in important moments. My respect to Janko Tipsarevic, because he's playing really good and having a really good season the last year and this year also."
Tipsarevic also lost in the 2011 quarterfinals, and this year reached the third round at the Australian Open and Wimbledon and the last 16 at Roland Garros.
"It's not maybe the quarterfinal (the crowd) wanted to see, without Rafa being there or whatever, but I think David and me -- and I'm not trying to over-exaggerate anything -- played the best match of the tournament," he said.
The semifinals could be even better.
Murray, beaten by Federer in the 2008 final, is wary of the danger posed by Czech sixth seed Berdych as he bids to become Britain's first male grand slam champion since 1936.
"He's a huge hitter of the ball. Even if you want to dictate points and be aggressive, he can take that away from you because he's such a powerful guy," the Wimbledon runner-up said after his quarterfinal win over Marin Cilic on Wednesday.
"You need to use good variation and try not to give him the same ball over and over, because he likes that."
Meanwhil, the women's semifinals will take place on Friday as world No. 1 Victoria Azarenka faces French Open champion Maria Sharapova in a rematch of the Australian Open final.
The second clash sees Wimbledon and Olympic champion Serena Williams continue her bid for a fourth U.S. Open title against French Open finalist Sara Errani, the first Italian woman to ever reach the last four in the hard-court tournament.
Errani is already through to the women's doubles final with compatriot Roberta Vinci, beating eighth-seeded Spaniards Nuria Llagostera Vives and Maria Jose Martinez Sanchez 6-3 6-2 on Thursday.
They will play Andrea Hlavackova and Lucie Hradecka on Sunday, with the Czech third seeds winning 7-6 (7/2), 6-4 against Taiwan's Hsieh Su-Wei and Spain's Anabel Medina Garrigues.
Russia's Ekaterina Makarova teamed up with Brazilian Bruno Soares to win the mixed doubles title, defeating Czech Kveta Peschke and Poland's Marcin Matkowski 6-7 (8-10) 6-1 12-10.