On isotropic I play with the point counter enabled. Some people think this is cheating or frown upon it...I see where they're coming from, I guess, but I find that it just removes tedium on my part, since I can always count cards on paper if I want. *shrug*
Every now and again I will find myself in a game without it enabled; for those games I typically count deltas ("I ambassador an estate, returning 2 to the supply...ok, I'm down 3...he ambassadors a curse, returning 1, now I'm down 5", etc.). This is basically what I do when I play 2p live as well, although I tend to play more multiplayer games live which tend to overwhelm my little brain -- I just play as well as I can and hope I have the most VP, since you have much less control over when the game ends in a 4p or even 3p game.
This is for the standard VP cards, including fixed-point kingdom cards. I treat variable point cards on a case-by-case basis:
Duke: track separately ("I'm up 6 and down 3-4 in duchies...ok he bought a duke, now I'm up 2 and down 3-4 duchies")
Fairgrounds/Silk Road: count # bought, figure out how much they're worth towards the end of the game
Gardens: last reshuffle before I think the game will end, see how many cards are in my deck, add the cards in hand, track deck size from there on out
Vineyards: track total vineyards bought, hope I have more actions (basically give up

)
Curious to hear what high-level players, especially those that choose not to play with the point counter, do. Especially when they play live.