It's hard to tell without any details on what you're converting (DVD, MKV from a Blu-Ray convert, etc), what machine you have and if you modified any of the settings. In general, "Apple Universal" or "Apple TV" are good choices.
I'm assuming you've done a search on handbrake hear, and I would also recommend to go to Handbrake's forums as well.
It would be good if someone could create a table of "from to's" to help people figure out the best way. I might post what I do to convert a DVD or a Blu-Ray.
Have you checked your CPU load? Are you pulling a file or writing to a USB drive? Have you rebooted? Did you try another movie? Did you recently update your computer?