We all hate delay of game penalties, and here is a fascinating (to me at least) bit of statistical analysis from Advanced NFL Stats. I got this from TMQ:
"In the common situation where the offense is about to be called for delay of game when it's not the closing minutes, and the offense spends a timeout, consider: NFL teams convert 67 percent of the time on first-and-10, and 55 percent of the time on first-and-15. So on first down take the penalty and keep the time-out, this doesn't do much damage to your odds of making another first down on that possession. But if it's third-and-1, then use the timeout: NFL offenses convert 72 percent of third-and-1 situations, versus 44 percent on third-and-6. There's a clear benefit to using time-outs to avoid a penalty once a short-yardage down is reached.

"So I would say: In the first half, use a timeout to avoid a delay penalty unless it's first-and-10 or second-and-long, or unless the time-out is your last. In the second half, use a timeout to avoid a delay penalty only on third-and-short or fourth-and-short when you intend to go for it. And at any point in the fourth quarter if it looks like you may be trailing within one score in the closing minutes, all your timeouts become much more precious than five yards."