i have a tradition to replay FNV on a yearly basis. every year i come up with a fun build/ challenge to self-impose in order to make each playthrough feel more unique and fresh. of course, these playthroughs are all modded to hell and back, which lets me get even more creative with the challenges.
this year, i did a playthrough where i made it so Stimpaks are auto-used whenever i took any damage and disabled healing from foods.
since you look to avoid going through the hassle of modding the game beyond the NV guide, i could still recommend you consider build challenges where you limit yourself to only using a specific set of weapons, like, for example, "pistols only".