A 3.5" would be great, but honestly, a 5.25" would be almost as good. Most computers still come with DVD drives. That means that most cases still have the drive bay for a 5.25" device, yet most people don't use their DVD drive. On most of my computers, I would probably use and Amiga more than I would the DVD. In fact, I have mostly moved to a single USB dvd drive passed around the house when needed.
The key would be to be able to pass the keyboard/mouse AND display into the PC itself. Dedicated ports would be good, but being able to click on a window in your primary OS to bring up a window that displayed the output of a hardware Amiga would be cool.
Best of all would be to have two joystick ports on the front, AND having the joystick data passing bi-directionally to the PC connection. That way you could use 9-pin joysticks as HID devices, and PC joysticks to control the hardware Amiga.