Scottish giants Rangers and Ukrainian heavyweights Dynamo Kiev were the biggest name casualties after the third qualifying round of the Champions League second leg matches on Wednesday.
Rangers failed to defy history in overcoming a 1-0 loss at home in the first leg in drawing 1-1 against Malmo in Sweden to bow out 2-1 on aggregate - their cause not helped by finishing the match with nine players.
The Scottish side had not come back from a home defeat in the past 55 years to win a European match.
Dynamo Kiev - semi-finalists in 1999 - never looked like overturning the 2-0 first leg deficit against Russian side Rubin Kazan and went out tamely losing 2-1 on the night leaving the victors within sight of their third successive appearance in the group stages.
Another former regular group stage performer Norway's Rosenborg also went out as they lost 3-2 away at unheralded Czech side Plzen to go out 4-2 on aggregate.
That trio joined Greek giants Panathinaikos in being surprise losers - Panathinaikos had lost a seven goal thriller at home to Danish side Odense on Tuesday to bow out 5-4 on aggregate.
Rangers were already up against it after their home defeat but the last thing they needed was to go a man down as early as the 18th minute when Steven Whittaker saw red for an off-the-ball incident.
However, the ten men levelled the game on aggregate in the 24th minute through Nikica Jelavic's superb volley.
Madjid Bougherra was ordered off in the 66th minute for elbowing Dardan Rexhepi in the head before Malmo's Ricardinho joined him for an early bath for a second bookable offence.
Rangers, with only one win in their past 22 European matches, were only 10 minutes away from extra time when Jiloan Hamad got a vital equaliser with a 20 yard volley to put the Swedes into the next round.
Ally McCoist's side will now join rivals Celtic in the final qualifying round for the Europa League group stages.
The Rangers manager felt his side had been the masters of their own demise.
"Obviously the result is a blow because we are out the competition but I thought for the majority of the game when we were down to ten and nine men the fact we keep ourselves in it was very pleasing," said McCoist, who stepped up from assistant manager to manager this season after the retirement of Walter Smith.
"But I don't think there is any doubt about it that indiscipline probably cost us the tie, certainly tonight."
Rubin erased any hopes of a Kiev comeback in the 19th minute by Vladimir Dyadyun with the Russian outfit - who are struggling to make a title challenge this season and trail leaders CSKA Moscow by 11 points - sealing victory through Aleksei Medvedev close to the final whistle.
Veteran Oleh Gusev got a late consolation for Dynamo, who with the other losers will have a final chance of playing European football this season when they enter the Europa League play-off draw.
The winners, though, go into Friday's play-off draw which will see four-time champions Bayern Munich, 2006 runners-up Arsenal, recent semi-finalists Lyon and Villarreal as well as Udinese enter the fray.