You need to strike a good balance between drinking and non-drinking tiles.  Too many of the former, and the players will get sloshed too quickly, limiting the number of times you can play in an evening.  Too few, and it doesn't seem like a drinking game any more! 

The answer here really lies in the crowd you're putting the game together for.  If it's strictly for laughs while you hang out, make more amusing non-drinking tiles, and limit the number of tiles that involve large quantities of drink.  Some tiles that are highly flexible - that let the players decide how much drinking gets done when it comes up, like Domino - are key to making a game that can be played in various crowds. 

While there can be a strong temptation to fit every entertaining tile into a set, you really need a good base of relatively simple ones, such as Give 2.  It's about pacing - you don't want every tile to be one the players have to learn or think about extensively.  Having a good mix of simple tiles in the set makes the more complicated ones even more interesting by comparison, too.

Also, be careful about the number of tiles that force players to remember conditions or special circumstances, such as the Can of Whoop-Ass.  A few are amusing, but too many are easily forgotten. 

If you're going to be playing with a core group more often than not, you're clearly going to want some inside joke tiles, particularly ones inspired by specific individuals.  If you're making a set only for play in a certain context, make the jokes as obscure and inside as you like.  But if you're going to want to take the set on the road, you'll need to make sure that any inside jokes are at least moderately entertaining for players who won't fully get it.