I don't know much about the earlier models, but I've been flying the Rs for the past three years more or less daily.
They're kind of a pain in any turbulence. If a butterfly farts three states away the thing starts to dutch roll. It's annoying as hell, but if you're flying an autopilot bird with a yaw damper it's much, much better.
The gear does need attention, both from the mechanics to keep it operating and from the pilot to keep it from breaking. Don't go whipping around corners at high speed and it'll probably be ok.
They're probably a little over-powered, which is a good thing. Makes 'em fast and they can carry a startling amount of ice. When you start seeing a little jagged outline of the wingtip strobe it's time to start doing something about the ice you've picked up, like get out of it.
The fuel burn is pretty depressing. I plan on 200 pounds/hr (34-36 gph in cruise) and I'm conservative. We don't have any way of leaning them out with much precision so we're probably running way more fuel through them than they need. I've had a few up to 13,000 and pulled the fuel flows back to maybe 26 gph total.
Run off of the mains (outboards) for 90 minutes before switching to the aux tanks (inboards.) Remember that excess fuel always returns to the main for that engine, no matter where it came from, so if you take off with full tanks and immediately switch to the aux tanks you'll just dump a bunch of fuel overboard.
Also, you can't cross-feed from an aux tank, which normally isn't a big deal but if you're flying over the boonies you do want to get fuel out of the aux tanks and into the mains (by running off of the aux tanks) in case you lose a motor and need to crossfeed to get somewhere.
That being said, the fuel system is harder to describe than it is to demonstrate. It takes about 30 seconds to get it down.
Um, other than that, I'd slow the thing down in turbulence. There isn't a spar AD on the 310s. Yet. I don't want to be the guy responsible for one being issued.
They can be a bit annoying to get slowed down to gear speed, especially if you have a particularly clean airframe or are lucky enough to be flying a 550 conversion, which makes for an awesome airplane.
20 inches of MP should get you into flap range, then the drag should get you right at gear speed. Drop the gear and 17-18 inches for a nice ILS at 130 knots or so. I think the book says 89 knots or something like that on short final but I've never been willing to go that slow.
Also, VGs are a great addition. They drop VMC by 8 knots or so and increase the gross weight. The downside is they stall sort of abruptly with VGs compared to the non-VG airframes. And, of course, with a higher gross weight and the same horsepower your single-engine performance is going to suffer.
As for single-engine stuff, I think they're pretty tame. Again, lots of power. We'll do single-engine go-arounds (at altitude) all day long, which isn't something I'd even consider in some other twins.
Enjoy it. They're good airplanes.