Shane,
given enough time, any seal can dry out.
I don't think you will have an issue with this.
I have PVC pipe on BOTH sides of the bulkhead and have never cracked one. I am careful with them, but they should just SLIP into the builheads. So they can be pulled out rather easily. Not like you have to kill yourself to remove them..........
Most folks drill towards the back corners.... My 180 has a 3/4" outlet and 1" intake on each side behind a weir (overflow).
If only two holes, I would do intake on 1 side and outlet on the other. However, if you are going to drill, you may as well have two holes on each side. Better intake to the filters and better flow/current from the dual outlets.
I know Tom and other's have the strainer come up from the bottom with no overflows. I think then you aquascape forever around it so it is hidden.
Since I have overflow and they are black, from the tank view they will never be seen regardless of my scaping...
Hope this helps.