I can honestly say that I never thought that Cap and Doc Ock would be a great match-up or anything like that.
Certainly not so that it would have "had to happen."
That got me thinking, though - in this day and age of characters being around for so long, what are the most notable match-ups that HAVEN'T happened?
Has Doctor Octopus ever fought Thor or Iron Man? Has Superman ever fought Two-Face or the Penguin? Have the Fantastic Four ever tangled with Loki?
What is the most notable match-up that hasn't happened yet?