So after reading countless posts and articles about various bugs, I want to share in case someone else is suffering from the same issue.
My problem: I was able to play custom maps, custom races, mods, etc, but when I started playing retribution campaign content, it would crash to the desktop. I tried validating the files, renaming the Documents/My Games/GalCiv3 folder, etc. to no avail.
Then I noticed there was a separate "GC3Crusade" folder inside My Games. After renaming that to GC3Crusade.old, it started up no problem!