Has to be Excel Saga for me. After a couple of episodes, even if I am on a major downer I will be giggling like hell and will just have to keep going - and I have done so many times.
Azumanga does similar, but for the kawaiiness was well as the humor (Osaka is of course, a classic)
Azumanga does similar, but for the kawaiiness was well as the humor (Osaka is of course, a classic)