There's an early 60s movie called The Last Man on Earth, which is an adaptation of I Am Legend, the same novel the Will Smith movie is based on. It's a story of a sole survivor Robert Morgan in a world where he tries to wipe out the vampire plague but learns a horrible truth about his solitary crusade.
I was surprised to see it stars Vincent Price as Robert Morgan. Price is such a distinctive actor with a theatrically sinister presence that I initially found it jarring to see him playing an everyman survivor type. Fortunately he's a very good actor and pulled the part off, and the twist at the end makes the cast decision make sense in hindsight. But at first it threw me for a loop.
If you want to see it for yourself it's free here:
https://www.youtube.com/watch?v=Vv2WUewBx8U
And here in a dubious AI colorization: https://www.youtube.com/watch?v=ovXE-vdSAL4
So what movies had this effect for you?