I generally do all the sidequests, cuz you know, they're actual gameplay. I practically never go for collectibles just for a 100% stat. I go for the minerals and stuff in Mass Effect, but not the Nirnroots in Oblivion. I went after the collectibles in Vice City and San Andres, because they actually give you stuff, but not the pidgeons in GTA4 where it's just for the heck of it.
I didn't go for 100% in Darksiders, cuz maxing out Wrath Cores is fucking pointless. I do go for all teeth and Riddler things in Arkham Asylum because they give you just enough XP to get you all skils (though half of them I don't use in fights cuz I suck at it).
I most definitely do not go for the stupid flags and feathers in AssCreed.
I do the secret exits and Star Road in Super Mario World and I'd go for the Star Coin in NSMBWii. Strangely enough, I still never have 100% in SMW. Not sure what I'm missing every time
The only game I truly 100%ed were the Donkey Kong Countries - again, they unlock secret worlds in 2&3. Technically I did more than 100% as they have 101, 102 and 103%, but ... you know
