Bayern Munich, last season's beaten finalists, play Arsenal and Juventus take on surprise qualifiers Celtic. Big-spending Paris Saint-Germain face Valencia.
But the fate of the two Spanish giants in Thursday's draw at UEFA headquarters attracted most interest and both were pitted against clubs with decades of European experience.
"I'm sure it's going to be a special game for him [Ronaldo]," said Emilio Butragueno, Real Madrid's director of institutional relations. "I think the fans will be very, very happy with this very attractive, thrilling tie.
"It will be a great experience for everybody. I would have liked to have played against United later in the competition but they won't be pleased either."
Barcelona vice-president Josep Maria Bartomeu told Spanish broadcaster Canal Plus: "Milan are one of Europe's greats and a club that commands a huge amount of respect.
"They are not going well in their league right now but they have some excellent players. They are not currently at their best but football changes from one day to the next."
"Over two games anything is possible," he said. "It's a beauty against one of the traditional European teams.
"In terms of quality it's going to be very, very tough."
Bayern Munich, beaten by Chelsea in last season's final, have a nine-point lead in the Bundesliga and were content to have drawn Arsenal who have struggled this season for any consistency.
"We can be satisfied with the draw, but we mustn't under-estimate them," said Bayern chairman Karl-Heinz Rummenigge.
"It's important we try to come away from London with a good result, score a goal there and lay down a marker. We can win it, and we start as favourites."
"In the Champions League, it always depen
