Hello,
I have a stepson who is going to be in Berlin. I am looking to see what hotels/hostels which people may suggest for two twentysomething males. I am looking for something clean and comfortable but standard amenities. If not a particular place then perhaps a sector/area to focus on for accessibility from the airport and interesting places. So basically a balance between cost and comfort.

What's their budget per night?

On two visits to Berlin, we were really happy to stay close to Alexanderplatz - once at the Park Inn right on the square and once at H2 Hotel. Both places seemed popular with younger travelers and I’m still thrilled when I see Alexanderplatz used as settings in movies. Transportation hubs and we ate outside every night.
Loved the World Clock:

https://en.wikipedia.org/wiki/World_...Alexanderplatz)

I’ve heard good things about the Circus properties. They have a hotel, a hostel and apartments. Fun, central neighborhood. https://circus-berlin.de/

I use Garden Living a lot, on Invalidenstraße, near Berlin Central (Hauptbahnhof). Easy access to Museuminsel , Reichstag etc, an interesting area too, just inside East Berlin when the wall was still standing.

Gorgeous rooms, with their own kitchen facilties and balcony https://www.gardenliving.de/en_index.php I've ever only booked courtyard rooms, those are very quiet and secluded.Very good public transport options!

Booking directly with them lowers the price, but I still have no idea about your son's budget per night.