When you expand, eventually you will have to hand over counties to someone else so you can stay within the demesne limit. In the following is what I generally do, but I don't know if this is the most effective way, so I'm asking whether there are weaknesses to this approach:
Pick a bishop (you can do with mayors, but I prefer bishop for the extra piety and because you can then appoint his successors manually with free investiture, also mayors tend to make the county inherited in an open elective, reducing your control over it) from a county already under your vassal, and give this bishop the new county. Your new county will then change to a prince-bishopric. this will cause the new prince-bishop and your count negative modifiers with each other, and busy themselves bothering each other instead of you. In addition, you'd want to give the new county to a bishop in another county FAR away to avoid them from accumulating too much power in one spot.
Give every new county you have this way and avoid having any vassal having more than one county to keep them in check. Avoid creating or usurping new ducal titles whenever possible to avoid the negative modifier. If they somehow created the title themselves (probably from a 2 county duchies), then DON'T give the other county under his de jure realm to him and give it to another vassal duke (preferably weaker ones) that already exist (perhaps by inheritances). If there aren't any, then you might want to suck the opinion penalty, unless it's too much to bear and you don't mind him growing a little stronger with that vassal you give him (most dukes with this problem usually only have one de jure vassal under him anyways). When you do have ducal titles which gives negatives on your vassals, give that duke title to ANOTHER bishop under another count somewhere faraway from that duke's de jure territeries, then proceed to give his de jure vassals into several other dukes to make them hate each other. Basically, make your vassals fractured between each other to make sure their loyalty towards you (by steering their hatred elsewhere) and to prevent any one of them becoming too large a threat when a new king is crowned.
Also, it's preferable or perhaps essential to have Medium Crown Authority to prevent them from actually waging war on each other, because that might still make one or several vassal powerful enough to be a threat later on. And later you might also want to make for High Crown Authority (don't forget to reduce the individual levy laws to minimum to compensate for the opinion penalty, the high crown authority law alone can give you decent enough levies) to prevent your vassals territories somehow went outside your realm. Usually this happens when they marry the wrong people(wrong for us, right for them, lol).