I keep it fresh several ways.
I chose really interesting real-world special flights. For example, a C-130 or C-5 to Antarctica.
Or I imagine I'm carrying cargo charter to the DoD (MoD for you Euros) to Shemya (there is a listening radar there for Soviet ICBMs).
Or there's an antenna farm in northern Thailand. Sometimes those places need a very quick spare part.
Or, I take some real-world event, like a tsunami or hurricane/typhoon, and I pretend to be doing SAR or Relief flights into the area, or refugees out of the area. Sometimes I do multiples - I'll fly in a 747 cargo to a main airport, a C-130 (or any civilian regional STOL type plane) from the main airport to a remote strip. Then I'll fly some helos to distribute the goods in odd places, or within the city.
Mostly though I fly on VATSIM.
The only drawback I have to VATSIM is time. It takes a long time to fly anyway in VATSIM of serious distance (because you cannot time-accelerate), and even if you fly short regionals it always is a long time in VASTIM because you have to figure out where there are controllers now, how long they'll be on - you don't want to invest 30 mins of pre-flight and one hour of flight time just to get to TOD and the freaking controller at your destination sgings off! Then after you figure a nice routing with controllers you have to google the charts, aerodrome diagrams, program your FMC (because nowadays it is a b1tch if you don't fly RNAV and FMC), yada yada yada... Extreme enjoyment but I find it's hard to do a "correct" vatsim flight in less than 1:30-2 hours.
For the past six months or so I've kept FSX extremely interesting, fresh, and engaging by purchasing the PMDG 747. Big fan. Huge. That thing is uber realistic. They have no-BS one hour and 90 mins pre-flight start-up states! Again, downside is you need time. There is an engine-running state, but still, you gotta get charts, figure out a route, program the FMC - you're still looking at 15 mins or so before even getting off the ground. I'm not grumbling, i find it highly entertaining, just giving an honest "cons" to all the "pros".
To keep FSX at it's most fresh, I sometimes combine all three:
Fly the PMDG 747 with a 50 mins pre-flight state, do it on VATSIM, and fly to or from interesting airfields.
For example, if the VATSIM controllers action is at LAX that day I'll fly into or out of that Air Force Plant 42 in Palmdale (where they made the SR-71 and U-2). Or if Boston is action I'll choose that air force base just west of Boston city instead of flying into/out of Logan.
Sometimes you get interesting conversations about your "special" destination/origin and missions, and you can just tell em 'nothing to see here, citizen, go back to your life".
I especially love flying into a very busy VATSIM session or "Event" as they call it without pre-signing up for a slot on their website. Sure, they make me hold a lot, or my departure can get delayed, but it sure is fun piling onto the ruckus at a busy event, especially unannounced. I also love to go into a busy terminal area during a well-populated Event and choose an airport near, but not the actual Event airport. For example, gatwick instead of everyone is at heathrow. Or some old Naval Air Station (now abandoned) around the Bay instead of SFO where everybody else is going.
One time there was a VATSIM Event for Daytona Beach coinciding with NASCAR Daytona 500. Now the VATSIM people didn't advertise it, but it was public knowledge that the President was going to visit the race, so when I flew in I was bumped to make room for Air Force One! Now usualy you're not allowed to play emergency or hijack or AF1 in the VATSIM, but since it was a real-life happening I guess they let it happen. There was an entourage of planes with AF1: AF2, some military cargo planes, a whole bunch. I was flying in some cars and parts for some of the race teams in my Kalitta cargo 747 and the controllers had the nerve to ask me to move to a different apron just as I was about to shut down the engines! Something about security and distance for the Prez, and whatnot!!
All those little oddities and misadventures keep it fresh. So in summary, the two biggest things are doing it live with real people (i.e. VATSIM) and getting a hyper realistic add-on (i.e. PMDG 747).