GUIDs are unique identifiers assigned to each unit when Torchlight first reads their .dat file. For most units, like monsters and NPCs, these only need to stay constant while Torchlight is running and they're active. However, items that a player has in inventory or equipped will be stored with a reference to the GUID. That means if the GUID changes, the item disappears. GUIDs appear to be set randomly, so if you don't fill in the GUID fields and a player downloads an updated version of your mod - or even just overwrites the mod with a fresh copy of the same version - the game will roll up a new set of GUIDs for your items and all of 'em that the player has will go poof. This will also happen if your item's GUID changes between versions, so try to avoid doing that too.
The only downsides (I know of) from including GUIDs are a file size increase of ~0.1kB/item (~100k/tier) and an impossibly minuscule chance of GUID collision
The only other kind of units that might be effected is player-type units, so this might be important for class mods too, but I haven't tested. NPCs and monsters don't have to remember anything from session to session AFAIK.