Etterna can be played in many ways and there are are no playstyles better than other, even though some of them are more popular.
The style with the biggest playerbase and the one Etterna's difficulty rating system is built around. Spread uses 4 keys, with 2 keys for each hand. It is not hard to learn and is very universal. It's biggest downside is the difficulty of trilling (quickly alternating fingers) with one hand compared to styles like index.
A style in which only 2 fingers are used, one index from each hand. Index players usually use arrow keys or a similar setup. It gives the advantage of speed but because of it's nature it is far less universal and playing charts made for spread is very hard with it.