Fifth seed Del Potro, whose match was shunted back to the late evening by the disruptions, was the first major casualty of the men's draw in the early hours of Friday morning when he lost 4-6 6-3 5-7 6-4 7-5 to 62nd ranked Spaniard Roberto Bautista.
On a third consecutive day of sauna-like heat and with temperatures climbing towards a peak of 43.4 degrees Celsius (110 Fahrenheit), organisers finally enacted the third stage of their "Extreme Heat Policy" after three hour's play.
Play was suspended for more than four hours on the exposed outer courts and, in a bizarre turn of events, the players had been back on court for less than two hours when a thunderstorm sent them scuttling back to the locker rooms.
Matches continued on the Rod Laver Arena and Hisense Arena throughout both stoppages, the latter lasting nearly two hours, after the retractable roofs over the showcourts were closed.
That allowed Nadal, Victoria Azarenka and Roger Federer to charge through their second round ties before the Rod Laver Arena was again exposed to the elements for Andy Murray to join them in the third round in the evening cool.
"For me, everything was fine," defending champion Azarenka said after beating Barbora Zahlavova Strycova 6-1 6-4.
"Played under the closed roof so lightning couldn't hit me. I didn't feel the heat. I didn't get sunburned. I was in the perfect conditions today."
Third seed Maria Sharapova had a tougher time, though, and a quirk of the rules meant her match against Karin Knapp was concluded in the full glare of the sun some 50 minutes after it was adjudged too dangerous to play.
The Russian reflected the confusion and anger of players over the last three days at a perceived lack of transparency over when the Extreme Heat Policy is put into force.
"No one really knows what the limit is," she said after closing out a 6-3 4-6 10-8 victory over the inspired Italian.
"Not the players (nor) the trainers themselves when you ask them when will the roof be closed."
Top seed Nadal took advantage of slightly cooler conditions under the roof to administer a 6-2 6-4 6-2 thrashing to plucky 17-year-old Australian Thanasi Kokkinakis.
The Spaniard, seeking a second Australian Open title, was delighted to be able to play indoors rather than in the furnace heat outside but more so that his serve had worked so well.
"It was important that the serve was there during the whole match," he said.
"It is very important here and it was working well."
Federer also picked out his "rock solid" serve as a highlight of his 107-minute 6-2 6-1 7-6 (4) demolition of Blaz Kavcic on Hisense Arena, where he had not played, under the roof or otherwise, for 10 years.
The four-times Australian Open champion selected a highly aggressive strategy to deal with the Slovenian world number 99 and it paid off impressively when he wrapped up the first two sets inside an hour.
"I think in these conditions and on the hard courts it's what we want to try to do, especially early in the tournament, without taking stupid chances," said Federer, who battled back from 3-0 down to win the decisive tiebreak.
"Of course, I was overly aggressive at times, but I'd rather be that than overly passive."
Murray displayed his customary brand of controlled aggression to beat France's Vincent Millot 6-2 6-2 7-5 in his fourth competitive match since returning from four months on the sidelines after back surgery.
Millot flourished an ironic bow after holding serve early in the third set but then proceeded to break Murray twice to lead 5-1 before the Scottish fourth seed reasserted himself by winning 23 consecutive points to finish the match.
"I didn't really care about winning 23 points in a row, I wanted to win the match," said the Wimbledon champion.
"I'm glad I finished it there, because very, very hard conditions. Even in the evening it was so humid."
Women's fifth seed Agnieszka Radwanska registered a two-set win over Olga Govortsova under the Hisense Arena roof but 10th seed Caroline Wozniacki needed a topsy-tury three to down American Christina McHale 6-0 1-6 6-2.
The weather disruptions led to some violent swings in the matches on the outer courts.
American Varvara Lepchenko won the first set but, clearly struggling in the morning heat, losing 11 straight games on her way to a 4-6 6-0 6-1 loss to Simona Halep.
"I think they definitely should have not started the matches at first place," she said. "I think they should have started the matches after the temperature cooled down a little bit because this is just too much."
Her compatriot Donald Young, though, said he had benefited from the weather-induced break in play to beat Italian Andreas Seppi 6-4 2-6 6-3 4-6 7-5.
"The suspension was good for me, he was totally in control," Young said. "A little bit of rest did me a lot of good."
Sloane Stephens, a semi-finalist here last year, prevailed through several swings of fortunes to beat Ajla Tomljanovic 3-6 6-2 7-5 and was just thankful to get off court unscathed after the storm.
"I was like, 'it's lightning!'" she recalled. "Where is the siren I don't know. Just kind of freaked me out. It was weird."