Welcome, Nick! I have a fairly new 45-70, and I can tell you it's stronger than I am. Yesterday I was shooting 300gr Hornady HP's and H335 for around 2100fps, and it's accurate - and my shoulder is still sore! I was also using Unique for some light loads, and IMR4895 with 405gr Remingtons; all were accurate except for some 350gr LaserCast bullets and 28gr 2400. Factory loads have also been great.
As stated above, some bullets may prove too long, but you can ream the throat if you want to go for really big loads. I did have a problem with 350gr Sierra's not wanting to chamber easily; the ogive must be too far forward, so even with some smaller bullets you may have to measure. I use the Stoney Point tool, and it works fine.
The only problem with 300yard shots is to learn the trajectory for the load you're using; once you have that figured out you're good to go. We were shooting a 5x5 peice of plaster board up on a mountainside at 350 yards, open sights, and once we had the drop figured out we were on it. With that big of a bullet, you just watch for the dust cloud to see where you're hitting!