A night that began with the shock of Wayne Rooney's omission, ended in bitter frustration and recrimination as Luka Modric and Cristiano Ronaldo sent Real Madrid into the last eight.
It was the controversial dismissal of Nani for a second-half foul on Alvaro Arbeloa that was the talking point.
At the time, United were leading through Sergio Ramos' own-goal and 2-1 up in the tie, following the 1-1 draw in the first leg at the Santiago Bernabeu.
The pivotal decision of Turkish referee Cuneyt Cakir turned all those hopes to dust, left Rio Ferdinand applauding sarcastically after it was all over and Jose Mourinho celebrating, the former Chelsea boss offering a fuming Sir Alex Ferguson a consoling pat before heading down the tunnel before the final whistle.
The bombshell of Rooney's omission and an ovation for Ronaldo as loud and as long as any home player has received this season set the scene for a match Mourinho said on Tuesday the "whole world would be watching".
Those who did would have been enthralled by a frenetic contest, largely played in midfield, which justified Ferguson's shock selection.
At 39, Giggs was not the obvious choice to shackle Ronaldo.
But the Welshman did a magnificent job.
And he was not restricted to defensive duties either. Though opportunities for both sides were limited, Giggs did find time to get forward, delivering one brilliant cross for Robin van Persie, whose acrobatic attempt to finish was blocked by Sergio Ramos.
If Giggs excelled, Danny Welbeck was the biggest threat, just as he had been in the first-leg.
His running from deep positions caused Real a problem, especially out wide.
It was Welbeck who provided that crossing opportunity for Giggs, having earlier presented Nani with a similar chance, which Fabio Coentrao flicked away before the veteran Welshman could pounce.
The one flaw in Welbeck's game is a lack of goals.
His effort in Spain was one of only two this season, and twice he wasted openings to break the deadlock.
The first came after Nemanja Vidic soared to meet Van Persie's corner, only for his thundering header to cannon back off a post, straight to Welbeck, who prodded the rebound straight at Diego Lopez.
Welbeck's second chance was also on the rebound, after Lopez had parried an instinctive effort from Van Persie.
The England man should have made Lopez work. Instead he drove his shot into the ground, which allowed the visitors' keeper to save.
Real had even fewer sights of United's net.
Gonzalo Higuain sent a decent chance wide in the opening stages but other than that, there was always a home defender in the way.
Ronaldo, after his heart-touching reaction to the reception he received, was extremely subdued, failing to make any impression with a free-kick perfectly located for one of those jaw-dropping efforts he seems to have made an art form.
The loss of Angel Di Maria just before the interval forced Mourinho into a tactical reshuffle which Real were still adjusting to when United struck.
Rafael's surge to the edge of the box had Real floundering and although Van Persie's shot was deflected away from goal, Nani had the awareness and strength to shrug Raphael Varane off it.
Welbeck got the faintest of touches to the Portugal winger's cross but it was enough to ensure Ramos' was firm enough to send it rolling into the net.
It all looked to be going to so well.
And then the roof caved in.
When Nani challenged Arbeloa for a bouncing ball inside his own half, he seemed committed and nothing more.
Cakir deemed it dangerous and after waiting until the winger recovered from a non-existent injury, out came the red card.
Nani was incredulous. Ferguson went ballistic.
And with good reason. Repelling Real with 11 men had been tough, with 10 it was bordering on the impossible.
Though they hung on grimly, with Rafael seeming to keep a goalbound Higuain header out with his arm, it took the visitors just 11 minutes to turn the entire tie on its head.
Modric struck first, with a viciously curling effort from 25 yards.
Three minutes later Mesut Ozil found Higuain, whose cross was turned home at the far post by the man United must have known would score.
At times like those, the £80million pocketed for Ronaldo is scant consolation, particularly as his enduring affection was seen in a refusal to celebrate.
The hopeless search for goals forced the 10-men down to the other end.
Rooney, by now a potential saviour, had a chance which he lifted over the bar from six yards.
With that shot sailed United's European hopes and, who knows, possibly Rooney's Red Devils career.