1. CPU operates at 3.3V.
2. High-current IO pins are capable of 15 mA source 9 mA sink.
3. Low-current IO pins capable of 3 mA source 6 mA sink.
4. The Due has 1 dedicated SPI port and 4 multipurpose USART / SPI ports. The SPI port is only routed to the 6 pin header used for ICSP on Mega but this is not used for ICSP on Due.
5. The Due does not have any EEPROM.
6. Due has lower power computing faster and flash sram bigger than mega2560.