Matt Bernier of Comic Tools lays out a great tutorial on the dos and don'ts of lettering in comics. A lot of it applies the common sense rules of typography and positive/negative space to word balloons. These are all really good ideas to keep in mind whether you're lettering by hand or using a font.
Read here --> This week: Balloon Shape.
He points out that while some examples of poor negative space are the result of the ease of computer lettering, even comics greats like Bill Watterson and Winsor McCay had bad lettering habits.
Also, in the comments, a brief discussion comes up about using hyphenation to break up words, which I've always considered a big no-no. But I love how Matt puts it:
"...breaking up a word with a hyphen to make it fit is like breaking your kid's feet to get him into smaller shoes. He'll fit, but he ain't gonna run too good any more."
It's a long thorough read, but a good one—with lots of doodles and samples to go along with it. HIGHLY recommended.