I quite agree with the OP. Prototype is probably my second-best game on PS3, and I stubbornly play it to this very day. I find things like its repetitiveness and the exhausting boss fights are part of its nature as an excellent stress reliever.
What I don't like of this sequel:
Graphics:
I loved the abundance of red tones of the original, it gave it its own character: now the city is more pleasant to look at, when you stroll around, but I can't see what's going on in the thick of a battle: too many colours, too many details. Enemies don't stand out from the background. For instance, they also added these glowing reds and blues on infected/blacklight soldiers, while the sky is a glowing green (in the yellow zone) and so on. The result is that it looks like a cartoon, or in other words, a poor design choice. Having every colour at the same time on screen takes away any mood, I don't know who thinks this is a good idea. And in a game with fast action like this, it only makes spotting your targets more confusing. Everything's blurring in a rainbow.
Ironically the backward graphics of P1 helped a lot in keeping things clear even in the mayhem.
Story and characters:
In the first Prototype game it was a bit messy, maybe badly delivered, but it took itself seriously. In P2 it looks like a parody of the same world.
In P1 Blackwatch and Gentek were effing professionals. Now they look like a ragtag of b-class villains. Just listen to the ridiculous Gentek speaker announcements or just every line of dialogue from them. It's like hysterical Dr. Evil & his useless henchmen.
Heller, on his side, certainly has a big heart, but a little brain.
Game mechanics:
The camera and movements are somewhat stiff: where Mercer was swift and almost liquid, Heller is jerky and cranky. The camera too.
Some attacks change your point of view, which is annoying because it breaks the flow (and also forces you to see that attack from the same angle every time. And in slow motion). Add a lot of unnecessary zooming in.
P2 wants to be like inFamous 2 replacing pigeons with Blackwatch soldiers (yep), and Arkham Asylum/City for the melee mechanics instead, but there are another two games that did it better. Also reminiscent of the Arkham games is the love for filling the screen with prompts and icon buttons, just for the sake of breaking immersion, because the average player has the memory of a goldfish and needs to be reminded what to press every 7 seconds. I personally hate the fact that you cannot disable the prompts, especially when they're so intrusive and all over the place.
When you jump there is no feel of pushing your body up, you seem rather to ascend or being lifted weightless, and you cannot chain jumps anymore, which was one of the core funniest things to mindlessly do in P1. You could literally bounce on the asphalt and concrete, it was just as dumb as it sounds but a lot of fun.
The triad spring-jump-glide has inverted controls for no reason, and no good IMO.
Oh, and changing the basic attacks from combos of buttons X & Y (both being chargeable) to just 'tap X or hold X for alternate attack' seems even more button mashing to me.
Web of Intrigue:
There is a much less inspired version now. They removed all the gory bits and replaced the stylish montage with generic white blinding flashes, probably just to mask the acting.