I always stay within 4 hours one-way. I had a Honda Fit that I would use to haul pins or smaller games, and although very reliable and fuel efficient, it would get very uncomfortable after anything more than a couple hours of driving. I could feel my sciatic nerve screaming at me. It has since been sold because it was simply too uncomfortable for long trips. I ended up buying a nice used Infiniti G35X as my daily driver to replace it. Much comfier and a lot more fun to drive, but can hold zero games, boo.
My normal game hauler is a 2000 Toyota Tacoma with the inline 4-banger. It has zero testicular fortitude and only 2wd, but comfy enough for long trips and has been exceptionably reliable. I have taken it to the bay area on numerous occasions to deliver/pick up games with zero problems, mechanical or spinal. On the downside, it was an ex-route operator truck and has 357,000+ miles on the odometer. Still runs like a clock but reeks like... well... an ex-route operator truck with 357,000+ miles on the odometer. Whenever I hauled machines to CAX or PAGG, I ended up smelling like a pack of Marlboros with a hint of dank warehouse funk by the time I got there, and I don't smoke cigs. Can't say I don't love the truck for what it is though.
BUT, that will all change in this week, as I am finally biting the bullet and picking up a new Tacoma TRD Sport double cab with the 6' bed to replace both vehicles. I anticipate the long trips being much more enjoyable very soon. Can't friggin wait.