cruizer,
How far are you trying to reach out and what size of target are you going after.
The 50BMG and 30-378 have a lot of power, but leave a lot to be desired at long ranges in regards to accuracy.
The problem that you will have is inconsistency, due to powder burn. Granted that they burn a lot of gunpowder, but due to the case design, they have a some what uncontrolled burn.
A great example is the 30-06 to the 308. The 308 offers a better burn consistency. If you look at what bench shooter are running(short range) you will see a lot have gone to 6PPC, or a round based on the design. A short, fat case offers the advantage of a more consistent powder burn.
What if boils down to is the bullet must have enough power to be useful at the target, and be able to hit the target. Nether the 50BMG or 30-378 will offer you sub MOA. And, both are more than a handful when your trying to tack drive at 600yds plus.