(1) Background: PETG (polyethylene terephthalate glycol) is a transparent, inexpensive, and versatile thermoplastic biomaterial, and it is increasingly being used for a variety of medical applications in dentistry, orthopedics, tissue engineering, and surgery. It is known to have remarkable properties such as tensile strength, high ductility, and resistance to chemical insults and heat, but it can be affected by various environmental conditions. The aim of the present study was to evaluate the topographical characteristics of four thermoplastic dental appliance materials in relation to water sorption in simulated oral environments (artificial saliva samples with different pH values). (2) Methods: The following four types of PETG clear thermoplastic materials were selected for the present study: Leone (L), Crystal (C), Erkodur (E), and Duran (D). In relation to the desiccation and water-uptake stages, their water sorption (Wsp) and solubility (Wsl) were calculated, and the surface topographies were analyzed on two length scales. The surface roughness was determined using a contact profilometer, and nanoroughness measurements were generated by three-dimensional profiles using an atomic force microscope (AFM). Statistical analyses (one-way ANOVA and unpaired and paired Student t-tests) were performed. (3) Results: After saliva immersion, the weights of all samples increased, and the highest sorption was recorded in a basic environment. Among the materials, the water uptake for the L samples was the highest, and for E, it was the lowest. In relation to water solubility, significant values were registered for both the L and C samples’ materials. After immersion and desiccation, a decreasing trend in microroughness was observed. The AFM high-resolution images reflected more irregular surfaces related to saliva immersion. (4) Conclusions: The sorption rates recorded in water-based artificial saliva were higher for basic pH levels, with significant differences between the samples. There were also significant differences related to the behaviors of the materials included in the study. In relation to roughness, on a microscale, the surfaces tended to be smoother after the saliva immersions, and on a nanoscale, they became more irregular.