That is highly personal, of course. I don't like to get rid of anything and I like a wide range of subjects. Slimming down my collection would be almost impossible or I would have to take a radical approach and pick only a few subjects.
For example, I love oddball cards. I have 100s of regional/food issue/Team Issue/SGA and other unique sets. I just love the fact that so many different oddball cards are made and you can find some really obscure players in some of these sets. Love them all, any team, any theme. I just recently picked up a complete run of Mothers and Keebler Cookie Dodger team sets. Lots of players in there that otherwise don't have mainstream Dodger cards.
Speaking of Dodgers, I collect Dodgers and must have somewhere in the neighborhood of 100,000 Dodger cards between singles, sets, autographs, oddball and such. This does include dupes and that is one way I could downsize.
My player collections have grown to massive proportions in some cases. Steve Garvey and Frank Thomas are the two biggest, each with several thousand + cards and items. The main Garvey card collection is housed in 12 supershoe boxes. I have a 5K box overflowing with Garvey dupes as well and that doesn't begin to touch on the magazines, oversized, and oddball stuff. I must have 30+ albums with various flat items (magazines, photos, etc)
I like Starting Line-Ups. I have several 100 of them. I like the old RC Cola cans. Probably have 100 of those. I like oversized cards and undersized cards. Lots of bulky stuff.
Autographed cards. I estimate I have 30,000 or so now, maybe more. Can't see myself getting rid of any but the 500-600 trade bait cards I have that I don't want. Can't get enough auto'd cards!!!
I guess what I am saying is that I don't see myself downsizing and thankfully I have the room right now. I could open a retail store right now and be OK for a while. Death may be my downsizing. This is a 4 way view of my card room, although these are slightly older photos. I have actually added more! That doesn't take into consideration all of my SLUs (20+ computer paper boxes) and 5K boxes (maybe 25-30) I stored under our stairs! Then I have more stuff in the garage...