The biggest problem, as Reignmaker stated, is stride length and type of movement. HOWEVER, I've seen mixed teams of all sizes. They will also probably wear very different sized harness and you will need to match up the neckyoke by adjusting straps = probably to the smaller horse. You will need to watch to make sure the larger one doesn't "bang" his knees on the neck yoke after the adjustments are made.
Here is a pic of my 45" stallion driving with a 40" mare. While he can and they did match strides at home, once out in the open on the road, he is a very forward pony and it just didn't work well. He became a VERY frustrated pony while trying to work with either of the two 40" mares. His stride was more horse like - with a tremendous reach at a trot. Even the longer reaching mare, on the road, could not keep up with him and he'd end up dragging her unless I was "on my game". Pairing him with the smaller mares was a LOT of work for me.
Here you can see their size difference.
Here's another that shows their size difference. They aren't striding together here. He makes Bit look TINY!!
Here you can again see they are in step, but that their striding patterns and body carriage are very different. He is a "finished" driving pony with a lot of single mileage and could have probably shown in harness. She has been driving for 2 years - but with little to no emphasis on collection and carriage - more on just "doing the job"... This was his first hitch as a pair and he was minding his "Ps and Qs" very well. She, on the other hand, has lots of pair driving mileage but wasn't happy to be paired with a stallion instead of her sister... She wasn't "mare-ish", just not happy about the change in driving partners.
AJ is also working with a work collar that is a good inch too small. That compromised his ability to work well, too. Before I could get a larger collar - he became sick and lost a ton of weight in Dec/Jan. He came back, but not all the way. Then in May of 2012, while playing in the wet round pen, he went down. Took a long time for him to get up and he "wasn't right". We explored several options - not fully sure what was going on. Doing a lot of testing and/or exrays wasn't really an option. We made the decision at that point to euthanize him. We didn't do a necropsy - instead burying him peacefully in our back pasture... He'd only been hitched as a pair a 1/2 dozen times. He was a riding pony extraordinaire! while our daughters were young/small enough to ride him. He'd turned 20 in March and spent 17 wonderful years with us - as a sire, a companion pony to older mares, a riding pony for a whoooole lot of children besides our 3 daughters and my driving pony.
AND YES, do join us over in the Driving Miniature Horses forum.