Diablo III Interview
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"One of the problems with the Diablo II system is that you kind of lock in with one or two skills. We really wanted to come up with a system that allows you to kind of experiment and try across different areas," he said. Runes are where the experimentation comes in. "You'll actually find drops that are runes out in the world that you can slot into a skill. That will not only augment a skill but it can change it complete... Depending on the type of rune that you got, you might take an ability and it might turn into a multi-shot ability, or it might turn into an area-of-effect ability."
Pardo also talked quite a bit about the potion system and how it sort of made the skills in Diablo II useless, especially since players would just quaff potion after potion in a fight. "What's the point of a healing skill if I can have my inventory [full] of a whole bunch of instant health?" However, the positive of that system was that it helped give Diablo II a fast pace. So now there's a health globe concept in Diablo III. "Monsters occasionally drop health globs that you can just pick up and recharge your health. So if you're killing monsters really fast, the action stays fast paced, and if you're not doing as well, you might have to an ability to escape away and then use a potion that can use periodically."