The first question is what you can afford and what you need. For short trips (<200 nm) you'll spend a lot of time and fuel getting to altitude. Actually, the 310 I fly with 300 HP engines will get to altitude pretty quickly, and is comfortable with an ice cooler. To get better climb rates out of the pressurized piston aircraft than I see in the 310, you will need to run the engines very hard, which most people don't do. At that point, the only real benefit is AC, which you don't need pressurization to get.
If you don't need pressurization (and it's really only beneficial on long trips), it's an expensive thing to have. Inconel exhausts, turbochargers, lots more places for air leaks within the induction and exhaust system, extra weight of the turbo systems, $25k windshields, the list goes on and on.
We have 3 kids, and the 310 is the only plane we take family trips in. On Sunday, all 5 of us flew from Ohio to Kansas City for our move there. Out of the blue, my wife said "This plane is awesome. We can all fit in here, all our luggage." A 310R with a Colemill Bearcat (300 HP 550s) would maybe be a bit better for us thanks to the nose baggage and the hunchback cabin. But even with the short nose, skinny body 310N that we fly, we do just fine.
Not all pressurized aircraft have AC. Not all aircraft with AC are pressurized.
If you do decide you want pressurization and cabin class, the Malibu has the benefit of being relatively easily insurable, even with low hours. It is an airplane that was designed with passenger comfort in mind, and it does it very well. It's also designed for the higher altitudes where it can get that efficiency. Excellent range. That said, I am surprised how low of time 340/414/421 owners are getting insured with no difficulty, even going straight from a weekend multi rating right into a 421. I don't recommend this, but it can be done.
I would not buy a 421. The GTSIO-520s have, especially recently, suffered a lot of expensive issues. Crankcase cracks are more common on those than the TSIO-520s. In addition, they seem to suffer more engine failures right on takeoff, which is the worst time, and 421s are very challenging to fly until you get the one engine caged. So, you have to ask yourself one question.