If the game tried to load more than ~3.5GB of data into RAM, it would instantly crash.
High-resource mods that add new textures or complex scripts are much more stable because the engine isn't constantly fighting for memory. The transition broke many existing tools, like the Hex Multitool and certain Cheat Engine tables, which were hard-coded for 32-bit memory addresses. The Present: Most popular tools (like the Borderlands Community Mod Manager borderlands 2 64 bit