If you format it as exFAT all computers (Windows and Macs) will see the drive except for Windows XP. There are some plugins to help the Mac deal with NTFS but our experience proves those add-ins to be unstable. If you format as NTFS it works great on all Windows machines, but Macs can only read from the device, they cannot write to it.
So what if you have a file bigger than 4GBs? Well, you have to decide what is the lesser of two evils. Typically these large files are either video files or restore image files (for restoring a computer operating system from a single image file). If you have a single file bigger than 4GBs then you must use NTFS or exFAT. If a single file is larger than 2GBs you need to have the device as FAT32. The one huge limitation with FAT and FAT32 is the single file size limitation.
These two formats are the best file system for removable drives like flash drives because they support the quick disconnect function and chances are very slim you will destroy the device or files if you unplug the USB without using the Eject function (in Windows) or Un-mount function (in Mac).
