Going straight up the Calder, Wycheproof is about the half-way point. There's nothing there I'd particularly describe as "boutique" or "beautiful".
Charlton is a little closer to Melbourne, but has a nice place called the Vale of Avoca B&B in an old pub.
On the Mildura side of Wycheproof, there's not a whole lot else until you get to Sea Lake. I can't speak for accommodation there, but Lake Tyrrell to the north of Sea Lake is an excellent spot for night star viewing or photography.
I live in Mildura and travel between here right up to Bendigo area for work regularly. I can tell you that there is nothing I would remotely describe as luxury in the middle of the trip or anywhere along the way. Honestly there really isn't anywhere that I would recommend - some of the pubs and motels are sufficient if you just need a stopover but that is it.
If we drive to Melbourne we do it in a day. It is easily doable. Takes about 6.5 hours with a stop or two to the CBD.
Thank you, I looked at The Vale of Avoca. It looks really nice. We have never stayed anywhere like that so we are looking forward to trying something different and having an adventure.
Stayed recently in warracknabeal country roads motor inn. Old dated exposed brick but comfortable accom and friendly owners. Also easy trip to pub down by river for dinner.