I mainly use spheres for their secondary effects, i.e., .05 magistrates and +1 diplomacy per sphere. So I usually just throw them on anybody where they'll stick, and I take as many as possible up to the point where I am spending over 90 prestige per sphere, at which point I start considering calling a halt to this parade. But here are a few considerations:
- You can put them on countries you'd like to protect - vassals and minors who are adjacent to you and serving as a shield are strong candidates - targets of your primary enemies may be the strongest candidates, or to be more precise, targets of countries you'd like to have a CB on
- Putting them on people you are planning to annex is a two-edged sword, because while they might keep others from stealing your target, they disappear when you annex so you will lose your .05 magistrates and +1 diplomacy
- If you put them on a country that is barely small enough to accept your sphere, if it grows in a peace deal or otherwise, you can lose your sphere
- People can't steal your sphere - multiple countries can SOI the same country - as long as the country exists and isn't too big for your sphere, it will stay til the end of the game
- If you are trying to become Emperor, you will blow everybody else out of the water in elections with your diplomacy score if you sphere everybody you can in the HRE. Also, the high diplomacy score makes it easier to do all kinds of diplomatic things like royal marriages and alliances, or my favorite, Enforce Religious Unity (Emperor only).