My general experience is that orientation of the fan really doesn’t matter.
The big things as others have pointed out is that you don’t want to go from 4 → 8 → 4 again. You can go from 4 → 8 → 6. If you can avoid the reduction at all, that is great. In my case I could get an 8inch exhaust port installed on the side of my house but I could get a 6 inch.
I do notice a difference between the T6 and the T8 in this configuration. The T8 can do the same job the T6 can but at a lower setting. During the cut I noticed the T6 would still ‘leak’ fumes. Basically there was a small odor. With the T8 cranked fully up, I don’t notice any smell at all, except off gassing that happens when you remove the material.
Also, you want the run of piping to be as straight as possible and as short as possible. As someone else pointed out, the extra curves in the pipe run will caused decreased air flow.