My longest running collection has been getting one signed Topps from each year (52-modern) of a HOFer. '52 of Ashburn, '53 of Spahn, '54 of Ford, etc... I've got maybe 25 or so, on up to more modern ones like an '83 Ripken. But the whole auto/forgery industry is getting so nasty, I've kind of lost heart.
Now, I'm just trying to get a nice card from most of the "legends" from the Ruth era on up. So far, I've got Ruth, Gehrig, DiMaggio, Mantle... wait, am I done?
I am also grabbing RCs from recent HOFers or likely HOFers while they're still "cheap". Pujols, Blyleven, Glavine, Raines, etc.
I also collect Harmon Killebrew, mainly because he is such a decent person. Musial too.