If you really don't care about the actual key you're playing in, I don't see any reason not to tune the Uke up (or down) to the pitch you find most suitable any particular instrument. But, if you're interested in keeping tunes in a particular key, or if you're playing with others and need to play in specific keys, then it's much easier (for me) to just default to Island Tuning, GCEA. And, keeping all my Ukes in that tuning means I only have to remember one set of chord fingerings. Of course, you could default to D or any other tuning and just use those fingerings.