At a New Year's Eve party in 1999, Aldrich Killian, then disabled, asks Tony to join his company A.I.M., and Tony brushes him off.
Thirteen years later, Killian turns out to be the mastermind behind the Mandarin attacks, after using Extremis to cure his own disability.
One careless brush-off in 1999 becomes the villain's whole reason for the plot.
Source: Wikipedia: Iron Man 3, Plot