Prototype vs InFAMOUS
Connection:
Both are the original main protagonists from rivaling action-adventure sandbox video games that were released in 2009
Both were normal humans with mundane professions (Alex was a Gentek scientist, and Cole was a bike courier) who were wounded in disastrous events they inadvertently caused (The original Alex was shot by Blackwatch soldiers after he deliberately smashed a vial containing the Blacklight Virus, while Cole was tricked by his future self into erupting the Ray Sphere), which would infect the cities they live in (Manhattan Island and Empire City, respectively) with a viral outbreak (the Blacklight Virus and the Ray Field Plague, respectively) and turn them into unnatural beings with superpowered abilities (Alex was a newly born sentient Blacklight Virus from the corpse of his original counterpart, while Cole became a Conduit). Because of this, they were labelled as terrorists and hunted down
Both have also been involved in conflicts against amoral organizations (Blackwatch and the Reapers, respectively)
Both are affiliated with a sense of good and bad karma, having started and progressed down opposite paths (Alex would save Manhattan from a nuclear threat but lose his faith in humanity soon after and become a villain, while Cole was canonically viewed as a terrorist by the local populace but bounced back to be recognized as a hero)
Both of them die in their second game's story ending (Alex is consumed by a vengeful James Heller, while Cole canonically sacrifices his life to stop the Beast and save humanity), their deaths of which would put a major stop to the viruses that threatened their worlds
Both have also had their voice actors changed for their second games