There are two main differences…
1. The TI-Nspire CAS handheld and software incorporates CAS (Computer Algebra System) as a tool for students to explore, evaluate and simplify expressions, numeric problems, and variables in symbolic form. Below are a few examples:

-Solve 5x + 2y = 10 for y [Answer: y = -(5/2)x + 5]
-Find the derivative of ln x [Answer: 1/x]
-Factor x^2 – 9 [Answer: (x + 3)(x – 3)]

This is similar to the difference between the TI-84 and the TI-89 where the TI-89 has CAS while the TI-84 does not.

2. The TI-Nspire Touchpad and Clickpad handhelds can be used with a TI-84 Plus keypad (available from TI – http://education.ti.com/84keypad) that, when used, allows your TI-Nspire to function as a TI-84 Plus. TI-Nspire in 84-Mode can be used side-by-side with a regular TI-84 Plus graphing calculator. You would use 84-Mode when connecting to a CBL 2 or LabPro.

In most other respects the two units function identically and can be used side-by-side in the classroom.

Product Information
TI-Nspire CX II Handheld (TI-NSCX2)
TI-Nspire CX II CAS Handheld (TI-NSCXCAS2)