Question about DS1621+ - 637995

The HDDs work no matter what size. It is best to use SHR - RAID then the disc size does not matter. With other RAIDs, the maximum size is that of the smallest disc.
Unfortunately I cannot answer the second question.

It doesn't matter, but some combinations are more favourable than others.
At Synology.com there is a very good raid calculator with which you can see what the effective sizes are. When inserting larger discs, you only have more space when all the discs of the same volume have been enlarged. You can usually connect additional discs to increase the size of a volume. The computer also helps here. I can't answer the second question either. It would never occur to me to store my data somewhere in the cloud. That's exactly why you buy a NAS.

Regarding the first question: HDDs of different sizes can indeed be used (check the compatibility list!). If you want to increase the size of a volume, this would be the way to go; the smallest disc in the RAID always determines the capacity.
Regarding the second question: a backup using Hyper Backup to the S3 cloud is possible, probably also to the Google Cloud, but I'm not sure about that. Azure is also available as a backup target.

I have already made the exact same change to larger ones
It's pretty easy with SHR
There are also online calculators for the effective size you will get afterwards.
For the 2nd question
You might have to have a look at Hyperbackup. Should work in my opinion. I use Hyperbackup to back up to a second NAS in a different location

Detailed information on the 2nd question can be found on the Synology website