I think I've watched Clannad and After Story 3 times each (I'm holding off on the VN until the Sekai Project translation comes out). I'm pretty sure each time through has been more emotional than the previous, for me. So, at least for me, knowing the plot in advance doesn't really make much of a difference to how much I enjoy it. I'm sure it diminishes that initial impact somewhat, but agreed with everybody else: it'll still be well worth watching the anime / playing the VN.