The problem with the Ford 460 is that while it is a good, durable engine, it's just so old now that, while any parts are still available, you won't be picking them up off the shelf at some auto part store in Podunk, Nowhere. Since most of us get RVs to travel, that's where most of the failures (fuel and water pumps, starters, alternators etc.) are going to happen. As Pianotuna points out, the early V-10s had a serious spark plug issue that was resolved by about 2004.
The nice thing about a V10 Class C is that while it has also been discontinued, it's still current enough (and shares many parts with the V8s and V6s) so that pretty much everything is a common stocked item at all the stores. I would have no problem getting a 460 truck as a daily driver at home but travelling with one of them would not be something I'd consider. You could end up having a trip really messed up waiting for something to be delivered. Don't know about you but here at home deliveries of all kinds have really gotten stretched out as of late.
Gas mileage isn't that much different from the V10 which is slightly better. We burn so much gas in RVs what's a mile or two? From what I hear, the new Ford V8 does manage to crack the 10 MPG barrier for a lot of drivers. I'll probably be looking for something with one of them next time.