The way my loop is running I'm coming down out of the rad from the left side of the case (facing side view), but the in port is on the right of my water block. I don't see why this would be an issue at all, but when I go to mount the water block can I just flip the middle part of the block itself so I can run my loop into it from the left side and out of the right. Hopefully that question is worded ok lol. I don't think this will cause an issue as long as I mount the rest of it together correctly.
If the block is labeled 'in' then don't take the top of and switch it around. Waterblocks are labeled in and out because they're designed to flow one way. Flow the other way can screw up your block, decrease flow and put uneeded stress on your pump. Just install the block upside down.