I have seen almost all the Star Trek content, and never developed a love of the ship structure. I like the Defiant because it doesn't look like it will snap in pieces when it turns a corner. It also proves you don't need to put the propulsion on sticks.
The manual for a licensed video game I once played claimed that the nacelles are mounted on pylons to separate them from the rest of the ship because they emit hazardous radiation when in use.
According to Memory Alpha, however, each of the Galaxy class' unusually large nacelles contains a control room for monitoring the warp drive's operation up close. This implies that it is safe to be not only near but inside the nacelle while the warp drive is running, which nixes the hazardous radiation theory.
Yeah, I think Roddenberry's initial vision, the nacelles were set apart from the living areas because constant close contact with the source of the warp field was hazardous (and who knows, in time the Alcubierre drive may prove him right).
I think over time there's just been this implication that the risk was reduced/eliminated thanks to advances in technology (spurred mostly by the narrative), and they stuck with the look basically out of AestheticTM.
Meanwhile, the Klingons put the nacelle inside their BoP. I guess they just YOLO it.
Design notes for the shows have said that nacelles usually work best in pairs and with at least 50% line of sight with each other, but they're not hard requirements. The nacelles in TOS were supposed to be detachable in an emergency but it never happened on the show, similarly to the saucer section.
I think the explanation for nacelle positioning they ultimately settled on during TNG was something about the shape of the warp bubble, but I'm not sure.