Upload sketches via USB Failed on 2560

Welcome

Please provide the schematic.

It would be useful if you could provide the complete error message. Please enable verbose output during upload and disable verbose output during compilation, perform an upload and post the output here using code tags (see How to get the best out of this forum).

How did you come to that conclusion? Loopback test (Loop-Back Test Instructions)?

Hook up a scope and check what is happening.

I'm not sure if I understand; the 2560 processor does not have USB functionality. If your FT232 provides a DTR output, you can use the FT232 instead of the 16U2; connect it to the Tx/Rx and reset pin of the 2560. Note that you need to have the current limiting resistors between the Tx/Rx of the 16U2 and the Rx/Tx of the 2560 in place (RN4A and RN4B in the reference design).