One - stay south of Sand Lake Road. There has been an increase in crime on the northern end of I-Drive.
Two - stay in a hotel with interior corridors. Two tourists were robbed this week on northern I-Drive, but in both cases, they had exterior doors that they had propped open while they were doing other things. Bad idea anywhere, even in Orlando. Hotels with interior corridors have more people watching what's going on and more restricted access.
Three - no matter where you visit, don't let your guard down. Be aware of your surroundings and don't take unnecessary risks. Don't give the bad guys an opportunity to make you a victim.
I worked on south I-Drive for several years, and it's a nice part of town. Very pedestrian friendly, lots of shops and restaurants. The I-Ride Trolley is a good, inexpensive way to get around. The passes come in 1, 3, 5, 7, and 14 day length and the trolleys run frequently. You can get to Sea World and Universal by trolley, so if you pick a hotel with a Disney shuttle, you're all set.