The first book to feature the character of Alex Cross is Along Came A Spider, which was first released in 1993, and made into a film starring Morgan Freeman in the lead role in 2001. If there was a true arch-nemesis to Alex Cross, then The Mastermind is it. The Mastermind first appears in Roses Are Red organising a bank robbery, and becomes a mainstay of the series in various guises. Gary Soneji first appears in Along Came A Spider, and features in a few more of Alex Cross’s stories over time.
The two most notable antagonists that Alex Cross has had to face are The Mastermind and Gary Soneji. The Alex Cross series is also notable in that several antagonists make recurring appearances in the books, prolonging the story arc over many year.