In that small form factor, PJRC.com has already developed the the Teensy++
. The AT90USB1286 chip is compatible with the ATmega1280 chip, with built-in USB connectivity. I use the Arduino IDE to program it and run Arduino sketches on it (see http://www.pjrc.com/teensy/teensyduino.html
Flash, SRAM and EEPROM are the same or better, but it only has 8 analog in instead of the 16 on the ATmega1280, and it has 46 digital I/O pins (9 PWM) instead of 54 digital pins (14 PWM). It supports I2C and SPI. So if you need the Mega for memory, you're fine, but if you need the maximum number of pins, you may be short.