My 4e campaign I've been running for about 3 months (9 sessions, 4 levels) has been pretty much entirely about travel and exploration. Here's what I do:
Before each session, I sit down and thing about interesting ideas. These might be:
Cool locations to explore (abandoned ruins, cursed sections of forest, spider-infested grasslands, etc)
Colorful NPCs (roaming bandits, Kenku walker-villages, extravagant hunting safaris, etc)
Interesting civilizations (Kenku walker-villages, ancient Libraries packed with esoteric tomes and lore, spirit-haunted fading kingdoms, etc)
Events (Godstorms, massive migrations, floods, etc)
Straight-up combat encounters (Young Red Dragon's sulferic bog-lair,
running battles with Hegemony riflemen, orc raiders, etc)
... or any combination of the above. I come up with 3-4 new ideas before each session and flesh out the ones I think are coolest/most likely for the characters to find. The rest go on back-burners in case the party goes "off the rails" or there's some big down time that needs some spice. Then I can just quickly skim my list and plop something down.
I also do a mix of "fixed" and "free" situations. For example, I might look at my campaign map, plop down "The Cursed City of Skajin" on the map or I might hold off the "Locust Swarm Devestation" and plop it down in the character's path when it seems appropriate.
I also have a daily "1 trouble" roll I make: Roll a d20 every morning, if it comes up a 1, they run into a situation from above. Works great if there's a 10-day stretch of wilderness they're travelling through and you don't have anything planned for it.
For combat encounters, if I figure it's going to be the only fight of the day, I crank the difficulty "to 11". I've gone as high as level + 7 for a single encounter to mitigate the power imbalanced of all the players figuring "this is our only fight today" and unloading all their dallies. 4e is designed to be a slow grind wearing down the party's resources over the course of the day's 3/5/7 fights, so if the party is only facing one fight, it gives you a chance to really throw something tough/epic at them.
So far it's worked great for me!
Of course, I've only ever run 1 non-exploratory/travel, "fixed location" game in my 16-or-so years of DMing, so coming up with stuff on the fly is pretty much second nature for me by now in case the above ideas fail me.