Currently, the only way to play with 4 keys (without remapping keys, which could be argued as cheating)
is to use 2 keys on a keyboard and 2 keys on a mouse (or a similarly odd setup).
When playing like this, there can be situations where you have to have a certain key unpressed for another key to register,
and tablet players cannot necessarily make proper use of this type of 4-key playing (although only few players are interesteed).
I myself would like to play (ranked plays) with 4 keys on the keyboard, both for better streams and for reduced risk of RSI.
i have already played around with macros for mcosu/unranked osu! maps, where i remapped z, x, c and v to LMB, RMB, LMB, RMB.
(although actually slightly differently to that to make sure every keypress registered)
i trained with this for ~100h across a year or so and my hands haven't hurt on any occasion, and have rarely gotten even slightly tired. Even on semi-long sessions of 5*+ maps, despite having so little training and my hands somewhat easily hurting with 2-key alternating on 5*+ maps. Furthermore my accuracy, escpecially on faster streams, improved. My 2-key alternating also improved during this, but i still prefer 4-key alternating.