Goddamn Bats: The most irritating units that you have to deal with in the GDI campaign are Devil's Tongue Tanks and Mobile Artillery. Devil's Tongue Tanks will always try to pop up in the middle of your base which required wasting money on building pavement (which prevents subterranean units while making your own units faster on it plus preventing terrain indentation from strong weaponry). Mobile Artillery was so overpowered in the vanilla version that it was badly nerfed in the Firestorm expansion which goes to show how hard it was to deal with them (And GDI got their own artillery too).
The Woobie: The Forgotten. The amount of hell they suffer through in Tiberian Sun and Firestorm ( where they lost two leaders) must take some form of record. In the end, they just give up on the rest of the world and go to the Red Zones where no one would follow.
Moral Event Horizon: Nod's endgame has Kane launch a massive terra(?)forming missile which instantly converts Earth into a Tiberian planet. In all likelihood this leads to the extinction of mankind and indeed all carbon-based life, and is made all the more chilling by the fact that Kane explicitly orders his soldiers to 'emerge from their bunkers and factories to partake in the technology of peace'. He knows what he is doing, and he wants to leave no loose ends in the creation of his 'virgin paradise'. The above arguably makes the Second Tiberian War Nod the most morally reprehensible faction in the series, far outstripping even the GLA.