Ever since Servants of Gaius, the Network System has featured an Enemy Flaw. In Sertorius we developed the concept further to create mechanics that help the GM determine the nature of the enemy and the enemy's motives toward the PC. Like other Flaws, for this to function the GM needs to work it into the game and keep track of the characters' enemies.
When players in my group take this flaw I immediately make an enemies list that includes names, stats, motives, etc. I also talk with the player to figure out how this person became their enemy. The purpose isn't to punish the player, but merely enforce the Flaw (which is important).
I also give each enemy resources. These should be reasonable and reflect the power level suggested by the type rolled. For example if the player rolls on the Enemy chart and gets a Mundane enemy, his lackeys (at least the ones he sends to deal with the PC) should probably be mundanes too unless there is good reason for them to be an Ogre or Sertori.
You also need to consider the nature of the grievance. Few enemies want their opponent dead (though that is a possibility on the chart). Mostly Enemies are worried about things like respect and honor. Be sure to keep the Enemy's plans to a scale appropriate to the grievance. No one is going to implode their personal empire over a minor misunderstanding (well most people won't do that). Again the results on the chart suggest what level the enemy would bring this to.
According to the Enemy Flaw, each adventure the Enemy has a 50% of making an appearance. This need not be done by adventure, it could be placed on a time increment if that works for you. The important thing is to pick a schedule and stick to it. Then roll before the game itself, so you can work the enemy into your prep if need-be.
This can take some thought depending on the scenario. You don't need to write down an entire adventure for the enemy, just develop some vague sense of the Enemy's plans.
Really you want to treat your Enemies as important NPCs because that is what they are. You also don't want their status as an Enemy to shield them from the physics of play. Enemies can die just like anyone else. The Flaw still exists though. The player will eventually acquire a new Enemy or his previous enemy's kin will seek revenge.
But what if you have multiple players with the Enemy Flaw and more than one enemy shows up during a single adventure? I suggest taking it case by case, but consider having them team up. It may well be in their interest to work together against the PCs.
Also don't be afraid to use cunning plans if the Enemy is smart. If your enemy's just show up every few games to shove the PC into a pile of dung as they chortle, you may not be making the best use of them. Certainly there is a place in Sertorius for the Biff Tannens of the world. But don't forget the schemers.
I suggest trying to find characters from history, fiction and film to serve as models to help you design Enemy's quickly. Salieri is an interesting model for an Enemy. He is a schemer, he is also a bit complicated and seems to have a certain image of himself that he believes in. Perhaps most importantly his motivation is envy. He is jealous of Mozart's talents and wants to destroy him because of this. That is a perfectly valid motive for an Enemy in Sertorius, the PC simply being better at something.
Enemies are well worth the work you put into them. They become recurring NPCs that keep things interesting and keep your players on their toes.