Falcao, whose price tag seems to go up with every goal, notched a hat-trick as last week's 5-1 quarter-final first leg win over Spartak Moscow virtually guaranteed Porto a place in the last four, provided they avoid disaster in Thursday's return in Russia.
Benfica also take a handsome lead into their second leg when they visit PSV Eindhoven after a 4-1 win in Lisbon last Thursday and Braga have hopes of making it three Portuguese teams in the semi-finals after drawing 1-1 at Dynamo Kiev in their first leg.
Thursday's other tie sees Villarreal visit Dutch champions and league leaders Twente Enschede with a comfortable 5-1 advantage and almost certain to face Porto in the semi-finals.
Only three teams have overturned four-goal first-leg deficits in European competition, the most recent being Real Madrid against Borussia Moenchengladbach 23 years ago.
Falcao's 10 Europa League goals, including two hat-tricks, make him the topscorer in European competition this season and he has also scored 12 in the Super League.
The 25-year-old has had something of a stop-start career but may have benefitted from moving to Europe in his early 20s -- with four full seasons of first-team football under his belt -- rather than late teens as so many South Americans do nowadays.
Falcao never played professional club football in his homeland, leaving Bogota club Millonarios as a 15-year-old to join River Plate in Argentina.
He made an immediate impact after making his River Plate debut at a 19-year-old, scoring seven goals in his first Argentine championship, although a serious knee injury slowed his progress after that.
Devastating Partnership
He has come into his own since joining Porto in mid-2009, scoring 60 goals in less than two full seasons and forming a devastating partnership with Brazilian Hulk.
Falcao, who also hopes to help Colombia win the Copa America in Argentina in July, said before the Spartak game that he wanted to stay with Porto, especially as they have already qualified for next season's Champions League.
"They make me feel good at the club and I'm very grateful for everything they have given me," he said. "I'm just thinking about finishing my contract well, and next year we have the Champions League ahead of us.
"Unless the directors take a different decision, I'm concentrated on this club and available for a renewal."
The worry for Porto fans is that the transfer-rumour machine has linked Falcao with nearly all of Europe's top clubs and past experience has shown it is almost impossible to resist when the likes of Real Madrid come calling.
Transfer speculation has also surrounded Hulk, centre back Rolando and midfielder Fernando among others.
Spartak admitted they face an almost hopeless task against a side who have won 24 out of 26 league matches and 11 out of 13 Europa League matches this season.
"We can try and reduce the deficit, but the way we played tonight it's probably not going to happen," said Spartak's Aiden McGeady after last week's game.
Twice European champions Benfica will reach their first European semi-final for 17 years providing they avoid a catastrophe against Eindhoven.
But PSV goalkeeper Andreas Isaksson said the Dutch team were not giving up.
"It's not an easy position for the second leg, but we have a chance and we're going to take it; we want to fight for it," he said.
Braga also have the upper hand against Dynamo Kiev who will be without former AC Milan striker Andriy Shevchenko after he was sent off in the first leg.
Dynamo chairman Ihor Surkis remained optimistic. "We will need to score a goal and see how the game develops," he said.
"Whatever happens, we have to play football and not sit tight in defence."
