Heard about a friend who tried to clear a squirrel nest from his panel without cutting the main power first. Sparks flew everywhere and he actually singed his eyebrows off, no joke. In my experience, shutting off that main breaker is the only safe way to handle something like that. Your mileage may vary, but I've seen enough close calls to always recommend it. Take that with a grain of salt, but it's a lesson learned the hard way for him.
Yeah, that's a solid point from @sarahj44... I learned a similar lesson trying to change a light switch without flipping the breaker. Let's just say I got a free, very loud alarm clock for a second. Always cut the main power, even if it seems like a small job.