Trams on the side of the ride have issues with street parking and and tight curves when they need to turn left. Probably some safety issues by modern standards.
Trams down the centre have less issues with traffic, but if building new these days trams and LR don't run in traffic lanes apart from crossing an intersection. Only legacy systems have true street running where the tram and cars share the lane. Centre running also allows a single set of poles and all tram related infrastructure to be concentrated in the one corridor.
For a modern design, centre running is by far the easiest and safest as its easier to keep the tram away from cars and people. In Munch I noticed a few locations where the platforms are off-set to minimise the overall width taken by the tram ROW. I assume in the past it was step out into the traffic, these days this is not acceptable and generally being removed.
I think if build Greenfield you could take a completely different approach and only have the doors open facing the centre of the road. This way you build a single island platform and less risk of people running out into traffic as they step off the tram. Yes there maybe a tram on the other side, but a single island platform can be slightly wider than a side by side platform because you only have 1 platform not 2, (often barely a pram width wide) and often open to the far more frequent traffic than trams. I know in EU when we get off we have to make sure the kids don't run out. All the services for the platform now only need to be installed once, not twice.
So for me, centre is the best and safest.