The Doc can manipulate the laws of physics and matter at the atomic level. He literally has the ability to do anything, whether or not the laws of physics permit it. This is a wrap win for Doc. There is nothing Superman prime could even due to even harm him, much less kill him.
Has he ever been proven to be able to transmute a herald, nevermind someone who is more powerful than teams of heralds? Or someone who has transmutation resistance feats like Prime?
Seriously though, what is Prime going to do to win this? Punch him to death? Manhattan sends thousands of clones to fight him while he sits and reads a paper and then bfr's him if he would ever need to or,,,,etc,,. The examples could be endless. The guy was basically a God that was still learning about his powers by the end of the movie and comic.
He was surrounded by a bunch of Batmans. The Silver Surfer would look immortal in that world too. Probably more so. The fact is, Manhattan has serious limits (only being able to stop 60% of the USSR's nukes). Superman is fast enough to stop them all in between playing 50 simultaneous games of chess.
I dont care with what or who he was surrounded by. I'm not using that as my example. I'm using the examples of how he created a precise construction on Mars with nothing more than a thought, how he createtd clones to do his bidding while he was busy with something else, how he could transport through space with a mere blink of the eye, how he recreated himself after being deatomized with no trouble at all, and how he was bored at the end of the story and decided he might just make a new species of life. As I said, he was still learning through the arc and only being able to stop 60% of the nukes is a low feat. Still wondering how he would even be hurt by Superman, Prime, or anybody like that.
Superman has hurt pure energy beings before, either through heat vision or his fists. Even someone as relatively limited as the Hulk can hurt people composed entirely of energy.
Considering how dense Kryptonian molecules are and the actual feats Superman has of resisting offensive molecular manipulation, I find it highly dubious Manhattan could turn Prime into anything. If you placed Manhattan on either Marvel or DC Earth, his implied power and actual abilities wouldn't be considered more godlike than people such as Superman or Silver Surfer.
When dealing with people with feats on the scale of Superman, Surfer, Thor, and high heralds in general, yes, I have no doubt that they can harm Manhattan based on who they have harmed. Granted, you still need the right power set or ability to do so, but I certainly don't think Manhattan would be able to stroll in the greater DCU or Marvel and not get humbled.