The physics of the giants of the Mythic West came about from seeing a Tyrannosaurus Rex skeleton at the Denver Museum of Nature and Science and Natural History. While large invertebrates are physically impossible (gravity pulls the innards down too quickly), the skeleton showed that vertebrates could indeed grow to three or four times the height of a human.
I then extrapolated to thick skins for the giants. Like the rhinoceros, I figured anything that large was likely to have a thick hide. That would mean that bullets, particularly fired from Civil War era rifles, would be minimally effective. They’d penetrate, but not automatically kill. Bullets would need to hit vulnerable spots like eyes or ears or joints.
I also decided that, like humans, giant knees would be particularly vulnerable. The tendons at the back of the knee have very little skin covering them and could be cut with a sword, which would disable the giant. Unfortunately for the humans, it took a few battles to learn this.
I also realized that anything that heavy would have trouble swimming. Whales and aquatic dinosaurs can do it because they’ve adapted to it, but with their density, giants would have trouble. That meant that major rivers became good blockades to their armies’ advances.
Finally, there’s the question of food. Anything that big would require substantial calories. I only briefly explored this in Sidekick, but will examine it more in future novels.