It depends on what kind of watertightness you're looking for, whether you're fully submerging the pack, or just looking to keep out rain. A lot of it is also dependent on the design and materials of the pack. Here are my experiences.

The most waterproof closure is the roll over type found on the dry bags, you just roll the top two or three time and buckle them together. There are a few packs that use this, but they're not all that convienent if you're accessing things a lot.

The top-loaders works really well in a vertical (standing) position, if it's not submerged. Usually theree's always an small opening at the drawstring, but that's usually covered by the flap. If submerged underwater though, water will pour in through there. If you get the larger bags with the extended collar, you could twist that around then fold it over and tie it off like a garbage bag, which makes it really waterproof, but access is a pain.

Zippers actually work really well too, when they're new. I've had my opsrey panel loader fully submerged underwater while swimming across a canyon pool, and the inside was almost completely dry (except for a few drops near the zipper opening). In a rain, they do pretty well, IF there's a good rain flap to cover them. Once they wear out though, water seeps through pretty easily.

Most packs aren't designed to be waterproof. Even with the best closure, water will still get in through the seams and material. A good raincover will do a lot to keep things dry though. If it's absolutely critical to keep things dry, don't depend on the pack to do it, put your items in a dry bag inside the backpack.