My V10 has 270,000 miles on it, and runs great.
Only repairs have been the starter relay and both forward oxygen sensors (which I think were a casualty of silicone contamination since they went out at the same time shortly after the Banks PowerPack install.)
For the past few years, 90%+ of my miles have been towing. I tow up to 18,000 pounds with it, which is over the OEM GCWR but I have upped the power with the Banks PowerPack and Diablo Predator tuner, changed it to a dually, changed differential to 4.56 Dana 70 gears, and upgraded the brakes accordingly.
Part of my tuning has involved raising the shift points and electronic rev limiter. It will sing along at 5500 for 15-20 minutes at a time without complaint. This allows me to maintain 65 on any mountain Interstate pass with a 12,000+ pound load.
The only negative side effect of the Predator tuner has been shorter spark plug life. Double Platinum plugs only last about 70,000 miles before the electrode is worn away. I put in iridium plugs this last time so hopefully they will last longer.
Some Triton motors have gone 1 million+ miles without major repairs.