Question about Fractal Define R5 Titanium

The fact that the cooler is rotated by 90° is not a big deal. You can place the rear fan at the top at the back.

As for the side fan:
It is by no means unnecessary. It can lower the temperature of the graphics card by up to 10°C, so it's very practical.
However, this is not my favourite position for a fan, (you could also place one at the very bottom in the front) because the side fan options usually don't have dust filters, and I think the side airflow interferes a bit with the 2-dimensional airflow.

What is to be achieved ?
Very quiet ? Very good airflow/good cooling capacity? Inexpensive?

Inexpensive: No additional fans.
Balanced: 2x Fractal Silent Series R3 (120mm, 1x) (one on top (out) & one in front (in)) Leave pre-installed fan.
High airflow: 4x be quiet! Pure Wings 2 (140mm, 1x) (one front (in) + one side (in) + 2 top (out)) pre-installed fans.
Super quiet: Pre-installed fans out. 4x Noctua Nf-a14 Pwm (140mm, 1x) (2x front (in) + 1x rear & one top-rear(out)).

(If there's enough money: Cover every possible slot with this one. Noctua Nf-a14 Pwm (140mm, 1x) ^^ )