With good support settings, orientation (rails up vs down) doesn't really matter as long as it's horizontal and not some weird angle. Rails up is less likely to have warping on the dust cover, rails down uses less support material (and is therefore a little faster).

But you really don't need to do multi-material to get clean support removal. Tune your support settings and your cooling and you can get clean support removal without wasting a bunch of time and material. Here's one I printed a few days ago, rails-up, in 3D Fuel Tough Pro PLA+.

I didn't do any clean-up other than just removing the supports. I could have probably gotten it even cleaner if I slowed the print down a bit, but this was only intended as a test mule.