A lot of anime's made me shed manly tears :|
But Ano Hi Mita Hana no Namae o Bokutachi wa Mada Shiranai, short; Ano Hana, made me cry the most :| At least I think it did, I can't really remember any other REALLY sad moments compared to that show. I mean, One Piece had its moments and other shows as well but I think that one had the most impact on me.