Fully transparent DAC/ADC (~30+ db better), digital volume control, user interface, bluetooth built in, etc.
The only reason I would get the 2x4HD is if I was planning a set it and forget it configuration for someone who only plays physical media (tapes, vinyl, etc). Don't get me wrong, it's still a capable device, but it isn't fully capable of transparant DSP up to CD quality. It will handle any lossy media fine and even with lossless media makes a general difference that most agree is worth it, but it's not quite able to handle it fully.
Fully active bookshelves are either bought as a package (Kali, etc) or are more of a lifestyle hobby (dipole speakers). Using something like the Flex lets you get a semi-active setup.
The subout only sends a line signal (non-amplified) so you would need either a powered sub or another amplifier to drive the passive sub.