Steven Lisberger has said he wants to make another Tron ("Tron 2" ... sigh) and is considering ideas (on the Tron DVD extras.) Here's my idea.
MCP said it was into boatloads of systems and was planning on invading military and government systems next. Presumably it was installing itself into these other systems as well. MCP continues growing, but so does Tron. Both programs are infiltrators henceforth, adding onto themselves until they become truly self-aware. Some revolution in personal computing could be responsible for this transformation, perhaps ubiquitous quantum computing modules or true random number generators (or both? are they contradictory? tea and no tea.)
This story is essentially the same sort of idea as the original because the MCP is the program dedicated to restrict access, while TRON is designed to provide access. Naturally the story can go a number of different directions from here, possibly adding in another character/program, having echoes of Flynn bouncing around the world (as the only user to have ever been completely inside the computer world, he may have had profound and permanent effects) interacting with the current characters. One idea that comes to my (geeky) mind is that TRON becomes too restrictive himself simply because it is the nature of monolithic systems that they do not cover all the edge cases, and has to relinquish control to provide ultimate freedom to other programs. This could be metaphorically based on the internet (peer to peer, possibly mesh networking), software (open source), or any number of other subjects I'm sure. I like the idea of the Open Standards/Open Systems/Open Source stance of course. It lets you approach the subject of copyright.
Er, of course, not if you make it at Disney...
Another possible plotline is synchronous vs. asynchronous logic, which is another sort of authoritarian vs. free action scenario - synchronous logic is easier to design and model, but asynchronous logic is more efficient - it's both faster and consumes less resources, at the price of complexity (any asynchronous I/O must be buffered.)
As computers have become more complex, and more ubiquitous, our comfort level with them has increased. My only real fear with a Tron sequel is that it will be made by Disney and targeted at the primary moviegoing demographic. The Disney label is not an automatic kiss-of-death but there have been no good Disney sequels since the "good old days", period. Any sequel that Disney has had any control of whatsoever has been ruined, not that my childhood memories are protected by copyright or anything. Anyway, the point at the beginning of this paragraph (sorry for the diversion) is that the issues could be more complicated as well - you've got the duration of the whole movie to get the point across. You could at least slide all kinds of themes in there - how about opportunistic encryption? IPv6?
All I ask is that the film not have the programs appearing in the real world. Manipulating it via connected devices is one thing. Stepping into it is currently cliched and thus annoying.