While I see your point in that zombies lose their zest once you get used to them, you lost me comparing this with RE. The thing with RE is that they went the outlandish and campy route. Mister X worked, so they brought Nemesis/The Pursuer. That worked, so they made Wesker the Terminator. That worked (sort of) so then they made the plagas, and so on, and for each boss came more outlandish and nonsensical mutations, and eventually we got boulder punching and COMPLETE GLOBUHL SATU-RAY-SHUNNN!!!
I would curb all that shit and try to keep it as grounded in reality as it possibly could be to have humans and other vertebrates infected by
parasite shrooms. That means no "speshul" infected, because that kind of thing isn't real. There can be hints of a hive mind, and of higher brain patterns, but there is no reaching out to infected as a society; the one thing these fungi have in common is that once it blows up the host is gone.
ETA: I have nothing against RE and I know it's not supposed to be hard science or anything like that, and a lot of those nonsensical stuff is pretty cool. I'm just comparing it to the first TLOU game in particular and a hypothetical more grounded approach that could have been. It's obvious someone did some research and it's obvious that Uck-ma'am was not the one that did it.