Internal mods are not really needed. They push the 603/606 to almost 500hp on stock inards. How much hp do you want?
I'm sure you could do internal mods, but it would be all custom.
Actualy if you are going for real big hp numbers, the 606 is the best choice. The injector is fitted in the center of the valves and it is a much more efficent design.
I guess if one wanted to really go nuts they could always lower the compression with custom connecting rods and pistons, make them lighter of course. Then figure out a way to make the head flow a massive amount of air, maybe much larger valves, with a custom cam to take advantage. Now slap on one of the largest Holset turbo's they make and with a lot of tunning, you should really have a monster.