I've been hunting whitetails exclusively off the ground for the last 10 years or so, and have managed to take at least one each year. I am going to use a hang on stand this year, though, at least for a few hunts. The main reason is that I've got a few great spots for one, and will only hunt them when the wind is perfect.
Like others have said, I do greatly prefer the mobility of hunting off the ground, not to mention the safety. One thing for sure, though, if you are using natural cover, you had better be willing to pass up on some close shots. When you are at eye level with a deer, they will pick up on any movement.
Take a look at this video. I was sitting on a Niff-T seat with my back to a small bunch of dogwoods and a big bunch of beauty berry; nothing in front of me. A group of does had just moved by my right at about 15 feet, but I had no shot. I heard this deer coming from about 100 yards away. When I saw he was not a legal buck, I slowly lifted my phone and recorded.
Pay close attention and think about when you would shoot. When he steps over that little log and stops, he's only about 6 or 7 feet in front of me. When this section of the video ends, he's about 12 yards, maybe a little less. Then think about how slowly you would have to move to not spook him. If you didn't already have your bow and body in position, you'd probably be out of luck. Your gear also needs to be as quiet as possible. Even an arrow making noise on the riser as you draw will give you away.
Incidents like this happen to me a few times every year. Most times, though, I'm much better hidden, and they don't even realize I'm there. I do also like to have some cover in front of me. I take a 6' piece of burlap and drape it up, high enough so that my arrow barely clears it. Kind of like this: