Damn Macedon, I say! Nothing stops a successful campaign quicker than a plague.

My main breadth of playing so far has been with the Greek Cities, and as them, the Macedonians are lightweights, the seluecids are entrenched but mediocre, and the Brutii are a paper tiger, but the Scipii always seem to foil me and grind my advance to a halt.

So, The Macedonians are annoying and hated for their plague, and the scipii for their resilience. Also, of course, playing as a Roman Faction, the most annoying enemies are your own allies. There's nothing worse than bringing up the rescources and recruits for a campaign to take a juicy territory, only to have it stolen out from under your nose by an ally you can't attack.

Of course, the Senate is also a bastard device of the devil for zeroing in on any faction I want to cultivate good relations with and then commanding me to the warpath.