Nadal, who completed a gruelling victory over Andy Murray on Thursday, looked out of sorts throughout.
Three-time Miami runner-up Rafael Nadal will play British fourth seed Andy Murray in Friday's opening semifinal.
Nadal's absence will lift Andy Murray, the Olympic singles gold medalist, to the No. 3 seed.
Djokovic's defeat means second seed Andy Murray is the highest-ranked player left in the draw.
France's Richard Gasquet will play Andy Murray after seeing off 13th seed Tomas Berdych 6-4 6-1.
At 27 years of age, Isner is older than Nadal, Djokovic, and Olympic champion Andy Murray.
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But Watson, who emulates Andy Murray's US Open junior triumph in 2004, proved just too powerful.
Their match had followed a classic encounter between fourth seed Andy Murray and Argentina veteran David Nalbandian.
In the tennis competition at Wimbledon, Andy Murray will takes on Roger Federer in the gold medal match.
Tennis had a record audience of 4.5 million viewers on the back of Andy Murray's US Open victory.
Third seed Andy Murray, who lost to Djokovic in January's Australian Open final, battled past Argentina's Carlos Berlocq.
Even more outrageous: In the semifinals, Djokovic needed five sets and nearly five hours to defeat Andy Murray.
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The Argentine won 6-0 6-4 to reach the second round, with Briton Andy Murray a potential quarter-final opponent.
As well as Djokovic and Nadal, the No. 2 seed Andy Murray, from Britain, is in action on Wednesday.
Wawrinka, who defeated Andy Murray in the previous round, fought off four match points before eventually being swept aside.
Bogdanovic will meet the winner of the match between Andy Murray and Tim Henman which takes place on Wednesday.
And fourth seed Andy Murray also cruised through, easing to a 6-2 6-4 victory over home favorite Andrea Seppi.
Players like Nadal, Djokovic and Andy Murray have been public in their dissatisfaction.
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No. 2 Andy Murray, the champion in 2009 and runner-up last year, beat No. 16 Andreas Seppi 6-2, 6-4.
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Andy Murray is also safely through to the fourth round after beating Lithuanian qualifier Ricardas Berankis 6-3 6-4 7-5.
Meanwhile, Andy Murray was pushed all the way before he defeated Amercian James Blake 6-3 6-7 (5-7) 7-6 (7-4).
World No. 2 Andy Murray, from Britain, took just 73 minutes to ease past France's Edouard Roger-Vasselin, winning 6-1 6-4.
Second seed Novak Djokovic and defending champion Andy Murray are among the big names to have already departed the event.
Bradley Wiggins won the Tour de France and Andy Murray won the Tennis Grand Slam in New York.
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Both world number one Roger Federer (fatigue) and Britain's world number three Andy Murray (wrist injury) are skipping the Shanghai tournament.
However, 28-year-old Gonzalez, who had overpowered all his previous Roland Garros opponents including third seed Andy Murray, began to fight back.
Both world number one Roger Federer (fatigue) and Britain's world number three Andy Murray (wrist injury) had already skipped the tournament.
The most streamed online videos were the tennis singles final matches in which Serena Williams and Andy Murray won gold medals.
And one of the other potential award contenders, British tennis number one Andy Murray, has tipped the driver to claim the prize.
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