The Xbox 360 supports up to 4 wireless controllers simultaneously for local multiplayer in compatible games (split-screen, party modes). No special setup—just sync each controller (Guide button → sync button on console).
You cannot assign two controllers to one player profile in a single-player campaign on the console natively. The OS recognizes only one "Player 1" input set.
Clarify your goal (local co-op, accessibility, sim rig) for a tailored solution.