John Isner could serve up a surprise against Del Potro
Nadal may also be in for a shock against Thiem
4pm Tuesday, Amazon Prime
It's the first day of of quarter-final action in the US Open and it could pay punters to expect a strong show from the outsiders in the opening last-eight action.
Even Serena Williams will need to be on top of her game in every match from this point on, but the best value could lie in taking on the big names in the men's singles.
Del Potro v Isner
There were numerous tips that 2009 Flushing Meadows hero Juan Martin del Potro may finally be well and truly back after he swept aside Borna Coric 6-4 6-3 6-1 in the last 16, but John Isner has won four of his last seven fast-court meetings with the big Argentinian and the American could extend that record.
Del Potro is the market leader by virtue of his higher rank, but the Tower of Tandil has been found wanting so many times in the quarter and semi-finals of Grand Slams that a lot of confidence in him has been lost.
Isner, meanwhile, is having his best season as a professional and it's just possible that the North Carolinian may be playing some of the best tennis in the world right now.
Even though he started slowly in his fourth-round clash with Milos Raonic, Isner was virtually in control of proceedings throughout.
After losing the opening set, he fought back to lead 2-1. Raonic then forced a deciding set, but with four of the five sets seeing one player charge into a 3-0 lead, it was Isner who timed things to perfection in set five.
That's not to say the 11th seed will be able to start as slowly against the top brass, but Isner is making few mistakes on court and, with vast experience on his side, that should only help his case.
He had to give best in his marathon Wimbledon semi-final against Kevin Anderson, but for now a first Slam triumph in his homeland would more than make up for his London loss.
Isner, one of the finest servers tennis has ever seen, is not going to receive many games from the oddsmakers on handicaps, so punters need to decide whether to back the outsider with a start or simply to win the match.
In many ways it's the biggest clash of Isner's long and distinguished career so both options can be backed.
J Isner +3.5 games
1pt Evs general
1pt 3-1 BoyleSports
Nadal v Thiem
Rafael Nadal defeated Dominic Thiem 6-4 6-3 6-2 in the final of the French Open in June but it could be worth siding with the Austrian in their first hard-court clash.
Thiem has beaten the Spaniard three times on clay, which is a pretty decent effort against the best slow-court player in the sport's history.
As we know, US Open defending champion Nadal is pretty good on hard courts too, although he was made to toil at times by both Karen Khachanov and Hamburg champion Nikoloz Basilashvili.
Thiem, who announced happily not long before the New York Slam started that his form was returning after a quiet period, stood well back to receive Kevin Anderson's serve in the last 16.
He'll be positioned further forward against Nadal, but this match will be won in the rallies and it would not be a surprise to see Thiem go close to matching his 32-year-old opponent.
Thiem gets a start of 5.5 games on the handicap and that looks worth taking and he could even progress to the last four.
D Thiem +5.5 games
1pt 10-11 BoyleSports
1pt 67-20 188Bet
S Williams v Karolina Pliskova
After a 6-0 opening set against Simona Halep's conqueror Kaia Kanepi, Serena Williams needed three sets to defeat the dangerous Estonian.
Things get no easier for the former long-time world number one when she meets Karolina Pliskova, who upset Williams 6-2 7-6 at this venue two years ago.
Williams will try a different game-plan this time, but Pliskova is going along nicely having recently linked up with Conchita Martinez.
The match could be close, so it could pay to expect 21 or more games to be contested.
Over 20.5 games
1pt Evs general
Stephens v Sevastova
Sloane Stephens, who is defending her US Open title vigorously as expected, faces what could be her toughest clash yet against Anastasija Sevastova, who may be playing career-best tennis judging by her results.
Stephens obviously is the likelier victor, but there was nothing in it when the pair met at Flushing Meadows last year and it could again be close.
Most oddsmakers give Elina Svitolina's conqueror Sevastova a start of 3.5 games on their handicaps but it could pay to take a shorter price and get another game on your side.
A Sevastova +4.5 games
1pt 4-6 Betway
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