Alright, I've spent a fair bit of time in that little Northern California town, and I think the central orbit really starts with Melinda 'Mel' Monroe. She's the nurse practitioner who rolls into Virgin River fleeing her past, and her whole journey with Jack Sheridan—the ex-Marine bar owner—anchors like, 80% of the series.
But it's very much an ensemble after a while. Preacher, the gentle giant chef at Jack's bar, and his whole saga with Paige and her kid is a huge thread. Then there's Doc Mullins, the crotchety old town physician Mel butts heads with and eventually works with, and his wife Hope, who is the town's... well, 'busybody' sounds mean, but she's the organizing force, the mayor in all but name. The Riordan brothers—Luke, Sean, Aiden, Colin—they get folded in too, each with their own book.
Honestly, it's a revolving door after the first few. You get used to characters having their moment, stepping back, then popping up again in the background of someone else's story. Jack and Mel feel like the town's beating heart you always come back to, though.