While the experience of programming them is obviously different, the 400/800 hardware seems to largely be a modestly expanded/fixed version of the 2600 hardware with a coprocessor stuck in front of it to offload all the "racing the beam" crap. Of course, I could be misinterpreting something.
What I meant was the graphics hardware rather than the systems in general, which I could have been clearer about. Looking at the registers for the 2600's TIA and 400/800/etc. CTIA/GTIA, they seem far too similar (while simultaneously being considerably different from other graphics hardware of the time) to write off as coincidence.
Really totally different. You're going from a machine that has 128 bytes of RAM to one with two orders of magnitude more (in the base configuration). You can use bitmap graphics. There are interrupts and they work. There is a ton of graphics hardware with a rich set of display modes, including characters and bitmaps. You can attach disks, modems and other devices (okay, the serial bus is slow, but there's an I/O system that makes it easy to use) and do development on the actual hardware. BASIC is built-in, but there are a bunch of other languages available if you don't like it. The sound is . . . better.
The platforms are orders of magnitude different in practically every dimension (except physical size :-) )