the monitor and the merrimack, two iron clads. met at hampton roads, slugged it out all day, neither taking any real damage. the hundley was a confederate submarine that was the first submarine to actually sink an enemy warship. it went down later in rough seas with all hands. the civil war was very much a preview of the changes that would come with wwi, large citizen armies entrenched against one another taking large casualties.
heres something horrific: in those battle lines that characterized gun-warfare from the early 1700s until the retiring of the smooth-bore flintlock in the mid 1800s many casualties were secondary. that is, when the ounce (~28 grams) of lead smacked into one soldier it deformed ("exploded"

causing bone fragments to injure soldiers around him.
back to the topic, the most damaging battle to the south was probably the early one where grant took the forts in tennessee/kentucky that controlled the tennessee river. if i were at home i could look up the name. those let union troops into the heart of the south, the iron mines in alabama and into georgia. of course, theres the big "what-if" lee hadn't lost gettysburg? could have wheeled into washington, perhaps forcing an end to the war.