There are many different factors that influence this for me but I will try to piece together the main ones. Let me start with order of adjustments I make when nymphing; depth, speed then fly. For me changing nymphs isn't about finding that magic fly. It's about giving the trout something different to look at than my last cast. There is such a variety of food underneath that the drift is the most important thing imho.
Given the right situation I would prefer to hike through a river system and not change flies. Things that I look for to fish this way are good to high flows, water temps above 46, uncrowded river, fish that aren't "spooky", good fisherman cover and a stream with plenty of fishable water. When I have all these things on a stream I am going to cover a ton of water. I feel comfortable that the fish are spread out and can be in every type of water (riffle,pool, pocket etc). Like I said this is my favorite way to fish, I love being on the move.
When some of these conditions go against me I will change the way I fish. The situations that happen the most are the low or cold water. When the temps go down below the mid 40s I tend to catch most of my fish in the same type of slower water. This ends up eliminating most of the stream as less productive water. The same thing happens when the water is really low. Many of the the normal hiding spots leave the trout vulnerable to predators. The trout end up stacked up in the deepest areas that are safe. In these situations I will fish each prime section really hard. I will make multiple fly changes and many different kind of drifts. It always amazes me how changing from a red zebra midge to a black will catch a trout's attention on the first cast.
Obviously a lot of this depends on you knowing the system. If it's my first time or it's still new I would probably just go exploring with the same two flies.
