It really all depends on how you pull it off. Somehow, Clannad has some of the funniest scenes I've seen in a VN, but it would also rank among the most tragic things I've ever seen. I forget the actual term for this (there really is one, I swear) but it's something along the lines of putting comedy in your story to make the tragedy that much more powerful. It's sort of like comic relief, but sort of the opposite. I really don't think you can be 100% serious, otherwise you're probably going to end up with some narm (Narm is an unintentionally cheesy scene that was supposed to be emotional.) However, 100% funny is alright sometimes, but most of the time it's hard to develop a plot and a conflict in your story if you never have anything serious. Now, looking at some of the anime I like best (Clannad, Higurashi, Elfen Lied) it seems to be 1:1 or even leaning towards comedy for the most part. But it complements the serious moments. Like, Sunohara in Clannad. Totally a joke character. Never does anything right, a failure at life, never takes anything seriously. However, when Sunohara is serious, it makes the reader/watcher go "Whoa whoa whoa. Alright, I think this is important."
However, as a sort of addendum, I've thought about it a bit, and I think I have played a VN that's totally serious. While a lot of Nitro+ games are pretty balanced, I can't think of one funny or silly scene in Saya no Uta. Make no mistake, SnU is really freaking good, and it manages to not really have any narm at all, despite being totally serious. So I guess that's possible too.
EDIT: (Thinking about it, the shock value of that game probably helps. Even when I want to laugh, I can't, because I'm still trying to comprehend what's happening xD)
As for what I prefer, I can't really say. I don't really like 100% funny, but other than that, just go with the flow. If you look back and you enjoyed writing your piece, chances are people are going to enjoy playing it, no matter the content. It's a bit wishy-washy, but just do what you like.