Master Prototype Trophy in Prototype 2
Complete the game on HARD difficulty.
How to unlock Master Prototype
This can (and should) be done in New Game+! Simply complete all of the main plot missions on hard difficulty, without changing difficulty settings. I recommend to do two playthroughs. Do the first one on easy and get all of the collectibles. Then you create a New Game+ on hard difficulty and mop up the remaining trophies. Hard difficulty itself is a piece of cake if you already have the upgrades from a previous playthrough. This playthrough will take you 5-6 hours only.
The hardest part is the final bossfight:
When fighting Alex Mercer on hard you won't have a chance to refill your health during the rounds, but if you die you will restart the current round with full health. Alex is quite powerful if you try to fight him in direct combat (especially when he is using the whipfist). A good tactic is to equip the hammerfist, jump up as high as possible and smash back down to the ground by holding down the attack button. It takes some while, but is a safe and easy method to survive the whole fight without getting a scratch. In round 1 and 3 you can also use the Whipfist to speed up the process. Keep jumping and perform long range attacks.
Check out the video walkthrough in case you are still having problems.