The first thing I did in organizing my romset was to archive anything that's not currently playable, insignificant clones, pinmame, mahjongg, quiz, foreign language, etc (with a few exceptions, of course!) That easily drops the list down to under 4000. ROMlister is great for this, especially if you have limited controls (no trackball/spinner/guns, etc.)
When I'm alone, if I'm not in the mood for a particular game, I find myself playing games at random from that "functionally complete" romset (usually via mameUI64, to be honest). If I come across one that is really great or might be notable in some way, I'll put it in the general gamelist that's available when friends are playing, via Mala.
That curated list is big, but not intimidating. Like shpongle's, I think my list is around 200-300 games.
If people ask if I have a particular game that's not on that list I can quickly bring it up, but I have to say that's a pretty rare occurance.