For the 325P25 in my truck I have it split up by zone: all zone 1 counties that use SC21 and ISP/IDOT districts in one system, all zone 2 in one, and all zone 3 in one. Eliminates some long distance talkgroup traffic (I do not run ID search mobile), but since I'm driving I'm generally only concerned with what's going on in my immediate area so it's not a big deal to me. I too let the GPS do its thing. Because of talkgroup limits I've had to omit some lesser used talkgroups but it's really only an issue with zone 1, the 500 TG limit is fine for 2 and 3 the way I have it programmed. I used to have a statewide SC21 system with only state agencies and a separate SC21 system with only local agencies but this took up twice the memory and would scan every site twice so I did some creative consolidation and switched to how I do it now.
On my SDS200 all ISP districts are just on the same quick key, IDOT has its own, ISTHA has its own, and so on. Nice and simple!