Is it safe to buy 2 times 2x8GB RAM, instead of 4x8GB RAM kit?

It seems to be a stupid question, but on many many website I see that the price for the 4x8GB RAM is higher than buying two times the 2x8GB, which is supposed to be equivalent. Of course, the RAM is the same, same brand, same frequency, same model and so on and so forth, since I buy it two times in a row. Starting from the assumption that I want to fill all my 4 DIMM slots, is it ok to buy 2 times the 2x8GB RAM instead of 4x8 one?

In the all cases that I know about, YES.

If the motherboard supports 32gb of RAM, then you're all set.

Yes, it's very nearly perfectly safe, even if they're different kits from different manufacturers running at different speeds, as long as you follow the directions in the motherboard's manual. The main things you need to watch out for are channels, CAS latency and other timings, and speed.

Motherboards have a lot of flexibility in how they can operate, but one specific design is that there are usually two "banks" for the memory. Within each bank, there must be at least two channels, they must be the same speed, and they must have the same internal timings. It is often a requirement that both sticks also have the same capacity, so you can't mix 4GB with 8GB in a bank (but you could do so between each bank).

Usually slots A and C are a bank, and slots B and D are a bank. Within each bank, you cannot mix single/dual channel, different speeds, or different timings. Assuming the parts are what they are labelled as, this means that if you buy two kits, consider putting each kit in the same bank to minimize the odds of anything happening. Banks on some boards are color coded; if you have two different color slots, make sure that sticks from the same kit end up in the same color.

If you're not sure what I'm talking about, check your motherboard's user manual for the limitations. In fact, there are professionals out there that will tell you that you should always pair up kits in the manner prescribed by your motherboard for the best chance of success.

Note that if you mix and match pairs, all of the sticks will be negotiated to run at the minimum capacity across all of the sticks. For example, mixing PC2400 and PC2666 will likely give much worse performance than using all PC2400 (for now, PC2666 and above is typically single channel, so half-bandwidth).

Do try to keep the sticks from the same kit paired, and do try to get the same type of specs for each kit, and you should be okay.