It all depends on what you want to do with the medium format camera. I have shot the Pentax PZ-1p, the Canon 1V, the Nikon F100, and the Pentax 645Nii medium format. From a size perspective, using typical lenses, they are quite similar while you are actually using them. Obviously, packing them in the bag is different but when you are out taking pictures there is not a lot to differentiate them. Ergonomically I preferred the Pentax 645Ni and ended up selling the Canon and the Nikon after about a year. (I still have the PZ-1p, but for different reasons.) I can handle the 645 handheld very easily and I am not a particularly big guy nor do I have big hands. Remember, this thing was one of the top wedding event cameras for a very long time, so it has some very good ergonomics.
For my purposes I love the Pentax 645Nii and the images I get can truly be stunning. However, it is a much noisier camera than the Canon was using the the motorized lenses. Lens focusing and film advance on the 645Nii are all noisy. But, amazingly, you quickly get to the point where you don't even notice when you are working with them.
I use the 645Nii for landscape, events (birthday parties, kids school plays, etc.) and macros. I do not do sports so I have no idea how it would work for that but it does seem just a bit slow. The image quality is great and I do not have to worry about computers at all (which suits me perfectly.)
Now, the bad. Medium format film is typically expensive, and developing is a lot more expensive, unless you do your own. 35mm is a lot less expensive per frame and you can usually get color negative stuff developed for very little money. As for using the Pentax 645Nii to completely substitute for 35mm...I don't know. I like both for different reasons. Besides, I absolutely love my results from my Pentax PZ-1p and my FA 31 and 77 Limited lenses and am not interested in giving them up.