Since Pi-hole is a private DNS server, upstream servers are required to answer queries for non-ad domains. There are several to choose from when running through the installer.
You can also now select and change these servers from the admin dashboard.
It's subjective; do you want the DNS provider to block certain content (parental filters)? Do you want enhanced security (anti-phishing services)? Do you want an unrestricted, untampered with connection? It's really up to you.
Level 3 provides the cleanest access. In the network administration world it's the go-to for upstream DNS. If you're into monitoring your network and blocking access to certain sites / services via DNS then OpenDNS / Norton would be a better alternative. The catch here is that you'll need to sign up for an account to get access to or control their services. Comodo isn't as intrusive as OpenDNS / Norton, but still provides security services. At the end of the day the decision is up to you. I prefer Level 3 but I also don't have any children or guests using my network.
There are two checkboxes for IPv4 and IPv6 each to select an Upstream DNS server. Is there any documentation available which explains for what the first and second checkbox is for?
Perfect, thanks for the quick reply! 
I was already wondering if I could enable special features with the checkboxes but that it is just related to the IPs of the servers was to easy ^^
I wasn't sure what to enter, so I chose "custom" and included the DNS servers from my ISP. What are the advantages/drawbacks to doing this?
Sorry if the answer is obvious, I'm a noob at Pi-Hole.
Depending on your ISP, perhaps none. Some ISPs redirect traffic to their own domains, or to partner domains, etc. Some filter requests without telling you.
My ISP (in the US) has a bad habit of replacing NXDOMAIN replies with their own reply, which didn't work for me.
On the other hand, many ISP's run good DNS resolvers and they are typically quite fast.
Comcast is my ISP so you can imagine that they're not the best.
What would be a good recommendation in that case? I need another DNS upstream server or most traffic won't get out.
You can choose from any of these that come pre-installed as web GUI options:
https://docs.pi-hole.net/guides/upstream-dns-providers/
Or, a better solution in my opinion, run your own resolver over which you have full control. It's a 15 minute install at most.
Thanks! I'll check those out!
