This to me was the least interesting colonial town (WHS or not) I got to see while travelling Mexico. There is very little to see and do; I think you could finish your visit within the hour without rushing things too much. Unfortunately, I had already booked a hotel room and had to stay for the night.
In fairness, what makes this side a bit different from other colonial towns, is it's orientation to the river. It's built towards the river and kept somewhat a feel of a port city, even though there isn't much left of the port. If this makes it a worthwhile WHS candidate, though, I doubt it.
Logistics
You can go to Oaxaca via Tuxtepec. There are busses running from Tlacotalpan to Tuxtepec. From Tuxtepec to Oaxaca you can either take another bus or search for a colectivo. The colectivo stand is literally around the block from the bus station (think the street was Melchor Ocampo, but better ask). The trip is long, but so is any trip from Chiapas to Oaxaca.
You can go by bus from Villahermosa via Cosamaloapan. From there you can take a regular third class bus to Tlacotalpan.