I play Paladin and have attack on the left mouse button and heal on the right mouse button and put resistences and procs on my armor and weapons. And I put evade on a thumb button on my mouse.

I think so far (Level 40) it kinda works, except for some tough bosses. I have a death count of 16 but only because I didn't pay careful attention to the damage the bosses dealt and adjust my resistences accordingly. Like swap from ethereal to chaotic for a single boss.

Is there someone who has mastered the onehanded (I mean only mouse, no keyboard) gameplay who can provide tips?

Idk if this is helpful or not but if you don't use the rotate camera(middle mouse) often then you could rebind swap weapon to that and have a backup weapon that gives you more two more slots since the left and right mouse button skills are tied to the weapon itself.
I'd put a buff and heal on a backup weapon and keep the main weapon for attacks.

Hope this helps!

Good hint. Thanks.