كتب : Omar AbdelAziz
The draw was believed to be fortunate for the English duo, who avoided some high-profile clubs in the last eight phase.
However, history suggests that outsiders Porto and Villarreal have what it takes to provide a tough challenge on Tuesday.
Manchester United vs. Porto
The Old Trafford clash evokes memories of the 2004 last 16 tie where the Red Devils were agonizingly eliminated by Jose Mourinho's side at the time.
Costinha's last-gasp strike sent the Portuguese champions through, in what was regarded as a major upset to Alex Ferguson's team. So this time the Scottish tactician is wary of his opponents' threat.
"At this stage it would be stupid for us to think it's going to be easy. We have to play full throttle," he said.
After two uncommon defeats in the Premiership, United came back to winning ways with a dramatic 3-2 victory over Aston Villa at the weekend.
Key defender Rio Ferdinand is set to miss out with a groin injury as Johnny Evans will deputize at the heart of defense. Striker Dimitar Berbatov is also out injured.
But Nemanja Vidic, Paul Scholes and Wayne Rooney are all set to return for the holders after missing the Villa game through suspension.
On the other hand, Porto welcome back top marksman Lisandro Lopez, who was suspended in the weekend win over Guimaraes.
Jesualdo Ferreira's side, who are unbeaten in the Liga Sagres since November 2008, will be without long-term absentees Jorge Fucile and Pedro Emanuel.
Villarreal vs. Arsenal
Villarreal will be looking to maintain their unbeaten record at El Madrigal when they host the Gunners in a flashback of the 2005-2006 semi-finals clash.
The Yellow Submarines have only lost once in nine encounters versus English teams in Europe. Ironically, it was Arsene Wenger's side who did the damage in 2006.
Ex-Gunners Robert Pires and Pascal Cygan will have something to prove against their former club, according to the French manager.
"They want to show you that they still have the quality and they are even more resolute to punish you," Wenger said.
"Everybody who loves Arsenal loves Robert Pires. For us he was fantastic."
Arsenal will have to do without injured strikers Robin van Persie and Eduardo, which leaves Wenger with the recently-fit Emmanuel Adebayor and Nicklas Bendtner as the only options available upfront.
Theo Walcott and Samir Nasri were passed fit, while long-term casualties Tomas Rosicky and Abou Diaby remain sidelined. Former Zenit ace Andrei Arshavin is ineligible.
Villarreal were rocked by the injury of star man Santi Cazorla, who will miss the rest of the season after fracturing his fibula at the weekend.