In the past, it was easy. If you flew a return, you could find deals, otherwise, you probably could not. That was in the days that legacy carriers still were proudly named flag carriers and low cost was non-existent. Anyone flying something else than a plain return was considered able to pay the hefty prices of something out of the ordinary. Yield optimisation was still simple in those days.
Now it's different. If I fly a return, I optimise flight times and airports. Our favourite hangout Lisbon has an awful low cost terminal, which we want to avoid at all cost. So sometimes we fly to Lisbon with our favourite low cost carrier Transavia (you don't have to go through the low cost terminal on arrival) but on the inbound flight we choose Vueling (well, we do not anymore, but that's a different story).
As I do not favour early flights or very late flights, it sometimes pays to make separate bookings. You have to take into account potential extra booking costs (easyJet spreads a fixed administration fee over the price of all tickets bought in a single purchase, Vueling doesn't seem to have a booking cost these days, Transavia hasn't had one in years).
You may use lowcostairlines.nl to find the lowest combined fares, but when you want to book them, take into account that this site often refers to online travel agencies rather than the airlines themselves. This will probably add costs to the purchase. Booking the single flights on the carriers' own website will probably by cheaper (but more time consuming).