Tomas Berdych sprung a surprise win over Roger Federer to end the Swiss star's US Open hopes, while a tearful Andy Roddick brought the curtain down on his storied career with a defeat to Juan Martin del Potro.
US Open: End of the line for Andy Roddick as Federer crashes out
But world number one Roger Federer will not face him in the semi-finals after the Swiss star was sent crashing out in a surprise defeat to big-swinning Czech Tomas Berdych.
The 17-time Grand Slam title winner, bidding to reach his 33rd Grand Slam semi-final and ninth in a row at the US Open, was beaten 7-6 (7/1), 6-4, 3-6, 6-3 by sixth-seeded Berdych.
"It couldn't be better," Berdych said. "There's no better moment so far than this one."
It was Federer's worst defeat at the tournament since losing to David Nalbandian in the fourth round in 2003.
There was no sign of the drama to come when Federer, who had not played since Saturday as a result of Mardy Fish's decision to withdraw from their fourth-round clash, broke to lead in the first game of the quarter-final.
But Berdych levelled at 3-3 before romping through the tie-break, taking the opener with his fifth ace.
The Czech went on to win the back and fourth encounter after breaking for 5-3 in the fourth set, and claimed victory after Federer put a lame service return into the net - the last of an uncharacteristic 40 unforced errors.
Meanwhile tearful Andy Roddick bade an emotional farewell to the US Open and his career at Flushing Meadowns this morning after a fourth-round defeat to Argentina's Juan Martín del Potro.
The 30-year-old, the last American man to win a Grand Slam event when he claimed the US Open in 2003, had already said this would be the last tournament of a 12-year career which yielded 32 titles and $20 million in prize money.
It also brought him the world number one spot as well as three heartbreaking Wimbledon runner-up finishes, before his prospects of a permanent place at the top table were swept away by Roger Federer, Rafael Nadal and Novak Djokovic.
"I've loved every minute of it — for the first time in my career I'm not sure what to say," said Roddick, who was in tears — as was model wife Brooklyn — as he addressed the crowd after his 6-7 (7/1), 7-6 (7/4), 6-2, 6-4 loss.
"I appreciate your support along the way. I know I certainly haven't made it easy for you at times."
Seventh-seeded Del Potro, the champion in 2009, booked a Thursday quarter-final date with defending champion Novak Djokovic.
"It was a really tough moment for me and for him. Last point of his life. The crowd was amazing," said Del Potro, who also defeated another former US Open winner, Marat Safin, in the Russian's last career match in Paris in 2009.
Murray reached his second successive US Open semi-final in dramatic fashion after Cilic squandered a seemingly comfortable lead to lose l 3-6, 7-6 (7/4), 6-2, 6-0.
Murray won 15 of the last 18 games to set up an encounter with Berdych. It was Murray's seventh win in eight meetings with 12th-seeded Cilic, whose only victory over the Briton came in the fourth round in New York in 2009.
But after twice serving for the second set, the 23-year-old Cilic's game fell to pieces and he won just three more games.
"I've had a lot of tough matches — everyone goes through them. We've seen Rafa, Novak and Roger struggle here," said Murray.
"There is pressure on you to perform well, expectations are high and sometimes you're nervous."
Top seed Federer, who has never lost a night match at the Open in 21 outings, and is playing in a 34th successive Grand Slam quarter-final, is bidding to become the first six-time champion in 87 years.
He is also attempting and make a ninth straight semi-final.
Serb second seed Djokovic was leading Stanislas Wawrinka 6-4, 6-1, 3-1 when the 18th-seeded Swiss retired after complaining of dizziness and handed Djokovic a 14th successive Grand Slam quarter-final place.
His tie against Wawrinka had been held over from Tuesday because of rain with the world number two ahead 2-0 in the first set.
"It was a difficult situation for both of us with the rain yesterday. We were here for 10 or 11 hours, warmed-up and then stopped. It was hard to get ready for a match that way," said Djokovic, the 25-year-old Australian Open champion.
Djokovic has reached his sixth successive US Open quarter-final by dropping just 20 games in four rounds.
"I'm happy with my performances. I played well against a quality opponent and I wish him a quick recovery," added the Serb, who played his match in front of just a few hundred fans on the 10,000-capacity Louis Armstrong Stadium.
Wawrinka has now lost 19 matches in a row against top-10 players.
Djokovic's fellow Serb, eighth seed Janko Tipsarevic, reached his second successive US Open quarter-final.
Tipsarevic brushed past German 19th seed Philipp Kohlschreiber 6-3, 7-6 (7/5), 6-2 and goes on to face Spanish fourth seed David Ferrer for a place in the semi-finals.
US fourth seed Serena Williams advanced to the semi-finals for the fourth time in five years with a comfortable 6-1 6-3 win over 12th seed Ana Ivanovic.
Williams, who lost to Samantha Stosur in last year's final, will now face Sara Errani for a berth in Saturday's championship match.
"It's going to be a good matchup. She is such a fighter. She's so strong and quick," Williams said. "I'm just so happy to be in the semis. It's so cool."
Williams has only dropped 16 games through five matches while blasting a tournament-best 41 aces, including 12 against outmatched former world number one Ivanovic.
"I came out really strong," Williams said. "Playing someone like Ana, the former No. 1, I knew I had to come out strong and play some amazing tennis."
The 3-6, 6-3, 6-4 result puts Sharapova into her first US Open semi-final since winning the competition in 2006.
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