This can certainly work in an RPG, but in a game that would prove rather problematic.
Can you elaborate on where you see the problems? Technically, it might be a challenge representing an shape-changing amoeba visually - that's mainly the issue I see. Game-logic wise I don't necessarily see issues - but I'd like to hear what you think.
The art monkeys can make them look the part, but the whole "shapeshift in a number of radically different things" is inherently limited by the format. How many shapes can such a character realistically take? I'd say half a dozen at best. If you want to account for every possible form a player could possibly take, you'd need an editor on par with Spore.
For example, in 4th edition D&D you have a race called the Shardmind: constructs consisting of shards of psionically charged crystal who sprung from the gate that keeps the Old Ones and Friends out. They can disassemble and reshape themselves on a whim, growing an extra head, an additional set of arms or whatever. You could use this to turn your character into a ladder or something so that the party can climb up to a hole, or a makeshift bridge across a gap. You could also store weapons inside your body if you want to get into a no-weapon place to murderstab someone.
Now imagine this in a cRPG. Either this would be heavily limited with a few pre-determined shapes or the "special" cases are pre-scripted set pieces and can only be used once a game and never again in a situation where it could be useful but is never used because plot.