1) Probably the most realistic and novel form of "it gets harder the further you go" is to use the historical model i.e. travel and adventure wear you down and you get weaker as you go along.
There are many, many examples in history of armies, expeditions, merchant caravans etc starting out hail and strong and by attrition on the road arriving tattered and staggering barely able to walk.
Normally, the fictional narrative has the characters and the challenges both start out small and grow increasingly power and more dramatic as the story progresses. In reality, the travelers start out strong but after the wear and tear of travel on people, animals and vehicles, fights, accidents disease etc, they get weaker. Challenges they would have brushed aside at the beginning can kill them towards the end.
It's a complete inversion and feels emotionally unsatisfying. In the classic dungeon scenario, it would be like having a boss in the first chamber, with the characters losing xp or levels as they progress (simulating injury) and in the very last room, getting wiped out by a couple of Kobolds. Yeah, it's realistic but we don't play RPGs to experience reality.
2) Changing climate. One earth traveling north or south 2000 miles can take you from mild temperate zones to tropical jungle or freezing polar regions. In either case the going gets harder. In a magical universe, each shifting climate would have it's own creatures or races to battle. As the characters got further and further from their homeland the combination of climate and the unknowns of dealing vastly different life forms, races, magics etc would increase.
There wouldn't be a focal point, just increasing maladaption and functional ignorance.
3) You could have a single enemy that grows in power overtime. E.g. The characters have an enemy who raises up an spirit entity from another realm to kill them. The spirit knows little of the story world so it starts out weak and naive. Each time it tries to kill the characters though, it learns a bit more. As the story progresses, the spirit and it's attacks (direct or via proxies) grow more and more powerful and sophisticated.
You could substitute anything for the spirit entity as long as it learned as interacted with the characters growing more threatening overtime.
The big advantage of this scenario is that its really about changes over time instead of space. You could set it in a travel scenario but you wouldn't have to. The characters could remain in a fixed location and just suffer repeated attacks, each more deadly than the last.