SQLite is just for calibre. Won't interfere with uploading books to ereader.
Custom book covers are *not* automatically added to metadata. You will need to use the "Update epub" plugin or do a epub->epub convert.
Calibre is *fully* compatible with *all current* ebook readers.
While you can manually move files onto your ebook reader, calibre handles the transfer quite nicely.
Many of us have many years of successful experience with calibre.