Had nothing better to do tonight so finally got my head around this. Having nutted out the One Control Honey Bee helped. And I have nearly finished building the Honey Bee so will know if these layouts will work shortly! I'm pretty confident about this one if the schematic is accurate.
I just built this and it works, so it is verified! I made a couple of changes to the layout so make sure you use the one above and not one you may have downloaded earlier. Pretty sure the electrolytic cap to Nature 1 should be 2u2, not 22uF like the schematic and that is how I have drawn and built it. it sounds right to me - I had a Honey Beest a while back.
So at least you know that if you build it as above it will work. :-)
If you are looking for a smaller board I think it may be possible but I like to keep box caps over 2-3 rows if possible and try to avoid having things span long distances. Plus it builds easily this way - I fitted it into a 1590B with top-mounted sockets easily.
If you like to connect grounds to the board there is no reason not to that I can think of. I come from an amp building background so I'm happy to keep as much wiring off the board as possible! When I first got into building pedals (because I couldn't afford to keep building amps!) I was surprised to read of people complaining about off-board wiring.
It's been very interesting for me to discover the differences between building pedals and amps. Layout in amps is a very different discipline - noise is more of an issue and grounding is almost an artform. It still surprises me that I can can stick parts all together on a vero board and still get a quiet result as long as I avoid ground loops.
So I still prefer to keep as much as I can off-board and almost star-ground to the input socket. No reason apart from habit. But in keeping wire length as short as possible etc I have very quiet pedals. :-)
There is no one "right" way of doing this stuff. Just recommendations and personal preference. I have my own likes - trying to keep box caps to 3 row spacing is one. They fit into a 3 row space with no bending of leads so that's how I try to keep it. A gap of two is ok in a pinch because you can hide the bent lead under the cap as long as the cap has space to go in between other components. Sometimes I have to put a cap over 4 rows and it bothers my OCD. So when there is a cap and resistor in parallel I never know whether to make the cap go 4 rows or the resistor 3 rows (which I also avoid). But sometimes these tough decisions must be made.