It was uploading sketches via ISP that wasn't working?
It's possible that that doesn't work on 2560, but does work on 328, because the program counter wrap-around happens differently on a chip with more than 64kwords of flash. On a 328, if you start in the "bootloader section" at 0x3F00 (where there isn't any actual code), it will execute relatively useless but unharmful instructions till it gets to 0x3FFF, and then wrap around to location 0x0, where your sketch actually begins. On a 2560, if the bootloader section starts at 0x1F000 and muddles along to 0x1FFFF, I'm not sure whether it will wrap to 0x0 (your sketch), or to 0x10000 (middle of nowhere, where it will eventually wrap again.)
I can't find this clarified in the documentation. Not that you need a "long" jump/call or to use EIND to change the high bit during normal program execution.