My wireless xbox 360 controller is turned on and connected, and when I am on the main screen of my game it works, but when I start playing I can't do a thing, including pressing start.

It sounds as if the xbox it self is locking up. If that is the case than you will need to contact Microsoft directly regarding the issue. I have also listed the steps to trouble shoot the controller as well.

1. Sync system first (By pressing the sync button on the system)
2. Right after you hit the sync button on the system, hit the button on the controller

Try replacing the battery's and or rechargeable battery for the controller. Repeat the sync process above.

Try another controller with your xbox or try your controller with a different xbox. Repeat sync process above.

If another controller works with your system than that would indicate that there is an issues with your xbox controller.

If your controller works with another xbox and no other controllers work with your xbox than there is a issue with your console.

For issues related to the xbox I would suggest contact xbox directly by calling 1800 my xbox.

If possible please rate the solution I have posted.