I think that we're talking about issues that may not really be important in the context of the OP's takedown rifle rig. Everything has it's pros and cons, and every trade off has to be weighed in the context of "is this important in this case?"
In the case of a takedown rifle you are by definition going to give a little something for the compact traveling package. The idea that this is something you will be putting together in a hurry to end some impending threat is out of context. For instantly ready defense, you carry a handgun loaded and on your person unless you are in a place where a heavy bore guide gun or the like is appropriate. Likewise, if you are going for a 500+ yard cold bore shot, you are going out with a rifle that is set up for that. You will have given up the convenience of the compact light weight takedown in favor of a long range hunting rifle. The '60s movie "Day of the Jackal" was fiction, and I decline to believe otherwise. A takedown rifle is something you travel with, then assemble at your destination. It's a gun more suited for the traveling, but still useful when you get there.
If you want to set up a Handi as a takedown, that's a great plan. I'd suggest cutting the barrel so that it's the same length as your stock and action. That way they fit into a case neatly. I'd suggest a screw with a finger tighten-able knob, but then again if you keep a screw driver in the case that's fine too. As for POI shift, you may get some but not likely enough to make a difference in typical game shots. Once you shoot the gun a bit, you will know what sort of shots you can make and what you can't. Your choice of cartridge (cartridges?) is going to make a much greater impact on how you can use this than the fraction of an inch shift from set up will. If you do it with (for example) 30-30, you will probably won't have enough shift to notice much within the range where that round is used. One inch one way or the other at 75 yards is still right in the boiler room on a whitetail. If you want to shoot something 500 yards away with it, you'll need comfortable shoes because your walking most of the way there before you shoot it
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So, what do you have in mind cartridge wise? Do you want something mid to large game-ish, or maybe a 22 Hornet to pop woodchucks and whatever other small game you come across? Maybe a two or three barrel set? Tell us more about the takedown rifle of your dreams.........