Whenever plague breaks out in a city, I tend to send a few of my spies to infiltrate it so that they get infected and I can use them as living biological weapons. If I want to eliminate a faction without actually declaring war on it, I send my plague spies to infect each of their cities and family members until they all die out and the cities become rebels. Once that's done, I move in and take over the cities which are usually filled with troops inferior to my own.

It's easy to do in vanilla (unmodded RTW) but a bit trickier to pull off in Europa Barbarorum.

I make sure to send enough spies into any town with wooden walls (or stone walls and a crap garrison) to make sure the gate's open. That way, you can siege, attack, and sack in the same turn.

As for assassins, I try to keep them busy assassinating enemy family members every turn, and if I run out, sabotage the enemy buildings that contribute the most to public order or produce the most annoying troops.

I use diplomats less than you do

I've always found the less sophisticated approach to be more successful, but if you have a mind to use them properly, spies, assassins and diplomats can make a dreadful mess of a faction. They come into their own most of all if you're playing a defensive campaign, otherwise it's just quicker and easier to capture territories from your enemies as it will make them weaker and yourself stronger. But this option isn't available if you're sat on the defensive, and you'll probably get bored with destroying army after army that your enemies are casually throwing together and sending against you every turn. So you have to find other means of taking the offensive to relieve the constant pressure.

I haven't much experience with defensive campaigns but I did do a sort of one as Greece once. Here my problem was trying to tempt many armies of Gauls into attacking the cities of southern Italy which I'd captured (I'd wiped Rome out and left its cities to rebel), but they wouldn't do it because I eventually had very impressive stone walls and garrisons of armoured hoplites with some Spartans waiting for them. What I did have was large and somewhat intimidating armies of Gauls laying waste to my territory.

So what to do? Well I recruited lots of spies and sent them into their cities to encourage them to revolt. Some did, and the Gauls had to fight to get them back, losing time and men in doing so. I also recruited assassins to bump off family members as well as destroy temples and so add to the chances of revolt, and I especially targeted buildings which posed the most threat to me - nobody likes to fight Chosen Swordsmen and Foresters. If you have a bulging treasury, diplomats can just bribe awkward armies to disappear or family members to come to your side. The result in my case was that Gaul was a complete mess. Its cities were revolting or threatening to do so, their economy was ruined as they tried to repair the damaged buildings, and their armies were constantly looking over their shoulders to put down revolts. My lands were quite safe.