Yeah, some of the factors that determine the preferred "handedness" of a rifle are based on practical considerations, mainly weight as stated above. But most of this is just force of habit. We want to hold the gun and cycle the bolt as we always have, even if there isn't really any logical reason for it. When you try something new and different, it takes some practice to learn to do it naturally, but this is usually pretty easily accomplished.
After a lifetime of shooting standard bolt action rifles and holding and cycling them as we are "supposed" to, I was worried when I first entered the Blaser system. The straight-pull action was different...the decocking safety was different...would I forget and mess up under pressure during a hunt? Nope. I quickly became comfortable with the system, and also find no disadvantage when I switch back to a more-standard rifle on occasion. Same thing with shooting an old Brno with the "backwards" safety...or switching from a pump shotgun to a semi-auto...or reeling a baitcast reel with your right hand but a spinning reel with the left, even though both are held in the same hand for the actual casting.
Getting comfortable and proficient with one system doesn't mean that you forget the older one, or that you can't learn the new.