I prefer horizontal on the walls as it seems more "natural" and "relaxing" (at least to me), to have them flowing around the room rather than pointing upwards -- particularly if you are doing a brick pattern -- and I wanted a horizontal accent stripe. When I think of rectangular tile, even large format, I think about bricks...and you wouldn't lay bricks in an upright orientation. However, if you are set on a vertical accent stripe, then it would probably look best with a vertical tile pattern. Or you could flip to horizontal, like I did.

For the floors, the easy way is to do squares so that you don't have to worry about which way they flow. Here is a picture of my master bathroom, which has 12" X 18" on the walls, 12" X 12" on the floor of the shower, and 24" X 24" on the floor of the rest of the bathroom; my wall tiles are laid in a stacked pattern rather than a brick pattern:

1. My tiles were all dead flat, so I could have laid them in any pattern. However, many large format tiles have some slight bowing which can cause noticeable lippage when laying them in an overlap pattern, and this is usually emphasized by the down-lighting from the ceiling fixtures which creates shadows on the walls of the shower along parts of the grout lines. You can test for bowing by putting pairs of tiles face to face and see if there are any gaps or rocking at the edges, or gaps (light) showing through the center. However, regardless of how flat they are, the best way to avoid lippage problems is by doing a stacked pattern because sets of tiles typically bow in the same manner (such as having a slight hump in the middle). The worst situation is if some of them are flat and some are bowed as you will have lippage unpredictably all over.

2. You talked about doing 2" X 2" mosaics on the floor, and that is about right for a standard drain in order to get the slope right, and have good traction from the grout lines. However, if you want to use a larger format tile on the floor, you can with a linear drain, either at one end of the shower or in the center because the floor can slope toward the drain in a flat plane.

Here is my shower floor with the drain in the center:

If you put a linear drain in the center, the total amount of slope the floor has to have is half as much as having it at one end. A large format shower floor also has the advantage of far fewer grout lines to keep clean, but it requires tiles that have a wet static coefficient of friction (COF) or 0.60 or higher so that there isn't a slipping hazard; the COF number should be on the box, or the spec sheet, or available from the manufacturer or distributor for the specific tile.